saralasin and Hypertension--Renal

Topics: Adolescent; Adult; Age Factors; Animals; Arteriosclerosis; Bradykinin; Female; Fibromuscular Dysplasia; Humans; Hypertension, Renal; Hypertension, Renovascular; Ischemia; Kidney; Kidney Function Tests; Kidney Transplantation; Male; Prostaglandins; Radiography; Renal Artery; Renal Artery Obstruction; Renin; Renin-Angiotensin System; Saralasin; Sex Factors

Topics: Adrenal Glands; Adrenergic beta-Antagonists; Aldosterone; Angiotensin II; Angiotensins; Animals; Blood Pressure; Disease Models, Animal; Humans; Hydrocortisone; Hypertension; Hypertension, Renal; Hypertension, Renovascular; Kidney; Renin; Saralasin; Teprotide

The role of the renin-angiotensin system in the pathogenesis of one-clip, two-kidney hypertension has been studied in man, dog and rat. Particular attention has been paid to peripheral plasma concentrations of angiotensin II in different circumstances; angiotensin II infusion has been combined with radioimmunoassay to construct angiotensin II/blood pressure dose-response curves. The effect of converting enzyme inhibitors has been studied, precautions being taken to avoid obtaining falsely high values for plasma angiotensin II because of cross-reaction with angiotensin I in these circumstances. The initial phase of one-clip, two-kidney hypertension is attributable to the direct pressor effect of the immediate rise in plasma angiotensin II. Subsequently, plasma angiotensin II is relatively lower, although blood pressure remains high. This upward resetting of the plasma angiotensin II/blood pressure relationship can be mimicked by infusing angiotensin II chronically at low dose. After reconstruction of a stenosed renal artery, or excision of a post-stenotic kidney, the angiotensin II/blood pressure relationship returns slowly to normal. In this second phase of one-clip, two-kidney hypertension, the long-term administration of saralasin, or of converting enzyme inhibitor, can also return arterial pressure to normal; brief administration of these drugs is less effective or ineffective. The results are compatible with, although they do not conclusively establish, an important slow pressor action of the renin-angiotensin system in the second phase of one-clip, two-kidney hypertension. This provides a rational basis for the use of captopril clinically in this condition.

Topics: Adult; Angiotensin I; Angiotensin II; Angiotensin-Converting Enzyme Inhibitors; Animals; Blood Pressure; Captopril; Dogs; Female; Furosemide; Humans; Hypertension, Renal; Male; Middle Aged; Potassium; Proline; Radioimmunoassay; Rats; Renal Artery Obstruction; Renin; Saralasin; Sodium

Topics: Adult; Aged; Angiotensin II; Creatinine; Electrolytes; Humans; Hypertension; Hypertension, Renal; Hypertension, Renovascular; Middle Aged; Prognosis; Renin; Renin-Angiotensin System; Saralasin

Topics: Angiotensin II; Angiotensins; Animals; Blood Pressure; Dogs; Enzyme Inhibitors; Humans; Hypertension, Renal; Hypertension, Renovascular; Renin; Saralasin

Topics: Adult; Antihypertensive Agents; Aortography; Arteries; Arteriosclerosis; Blood Vessel Prosthesis; Child; Endarterectomy; Fibromuscular Dysplasia; Humans; Hypertension, Renal; Hypertension, Renovascular; Kidney; Middle Aged; Nephrectomy; Radioisotope Renography; Renal Artery; Renin; Replantation; Saralasin; Splenic Artery; Teprotide; Transplantation, Autologous; Veins

Topics: Adrenal Glands; Aldosterone; Angiotensin II; Angiotensin Receptor Antagonists; Animals; Blood Pressure; Cardiovascular System; Diet; False Positive Reactions; Humans; Hypertension; Hypertension, Renal; Kidney; Posture; Rabbits; Receptors, Angiotensin; Renin; Saralasin; Sodium; Teprotide

Renal hypertension is better understood now as a result of the development of new laboratory techniques which permit the identification of the surgically curable forms of renovascular and renal parenchymal hypertension. The rationale for and efficacy of these new advances are discussed and a practical approach to the diagnosis of renal hypertension is offered.

Topics: Angiotensin II; Animals; Blood Pressure; Clinical Enzyme Tests; Humans; Hypertension, Renal; Hypertension, Renovascular; Renin; Saralasin

Topics: Adenoma; Adrenal Gland Neoplasms; Adrenocortical Hyperfunction; Catecholamines; Contraceptives, Oral, Hormonal; Estrogens; Female; Humans; Hyperaldosteronism; Hypertension; Hypertension, Renal; Hypertension, Renovascular; Male; Pheochromocytoma; Renin; Saralasin; Sodium

Topics: Adult; Angiotensin II; Animals; Female; Humans; Hypertension, Renal; Kidney Failure, Chronic; Kidney Neoplasms; Male; Middle Aged; Propranolol; Rats; Renin; Saralasin

Topics: Aldosterone; Angiotensin II; Aortic Valve Stenosis; Bartter Syndrome; Binding, Competitive; Blood Pressure; Contraceptives, Oral; Humans; Hypertension; Hypertension, Renal; Renin; Saralasin

Topics: Antihypertensive Agents; Humans; Hypertension, Renal; Hypertension, Renovascular; Kidney Function Tests; Propranolol; Radiography; Radionuclide Imaging; Renin; Saralasin

Topics: Adrenergic beta-Antagonists; Angiotensin II; Blood Pressure; Diagnosis, Differential; Diuretics; Ferricyanides; Furosemide; Humans; Hyperaldosteronism; Hypertension; Hypertension, Renal; Nitroprusside; Oligopeptides; Pheochromocytoma; Propranolol; Renal Veins; Renin; Saralasin; Stimulation, Chemical; Teprotide

Topics: Aldosterone; Blood Volume; Female; Humans; Hyperaldosteronism; Hypertension; Hypertension, Malignant; Hypertension, Renal; Middle Aged; Propranolol; Renal Veins; Renin; Saralasin; Sodium; Teprotide; Vasoconstriction

The complex hormonal action of angiotensin II in the long-term control of blood pressure or sodium metabolism, or in renal hypertension, is not completely understood. Structure-activity relations with analogues of angiotensin II gave information about the functions responsible for pressor and myotropic response in the molecule that led to the synthesis of competitive antagonists of this hormone. These antagonists, however, show variable agonist/antagonist ratios in different species or different tissues of the same species. This fact necessitates further work to induce tissue specificity. Although des-Asp1-angiotensin II ("angiotensin III") has been recognized as a hormone, its exact role in the biosynthesis of aldosterone is yet to be discovered. The antagonists such as des-Asp1-[Ile8]-angiotensin II or des-Asp1-[Thr8]-angiotensin II have provided important leads in this direction. Many of the biologic effects of angiotensin I have been attributed to its conversion to angiotensin II by the converting enzyme. Recent investigations indicate that angiotensin I itself may play a direct role; however, most of these studies were carried out by inhibiting the converting enzyme activity with peptides obtained from the venom of Bothrops jararaca. Since these peptides also potentiate bradykinin action, the observed biologic activities could be caused by either angiotensin I or bradykinin. Bsides, converting enzyme is no longer thought to be a single enzyme and its nature varies from species to species and from tissue to tissue in the same species. Renin inhibitors related to renin substrate or pepstatin are not freely soluble in plasma and are not effective under physiologic conditions. This points to the importance of renin inhibitors isolated from kidney or other natural sources. Thus, although the renin-angiotensin system appears to be an integral part of the problem of hypertension, characterization of various converting enzymes, roles of extrarenal renin, isorenin, tonin, and brain-renin, and the involvement of other humoral, neurogenic, and immunogenic factors should be pieced together to get a clear picture of the hypertension problem.

Topics: Aldosterone; Angiotensin II; Animals; Antibodies; Blood Pressure; Diet, Sodium-Restricted; Dogs; Hypertension, Renal; Macromolecular Substances; Muscles; Phospholipids; Rats; Renin; Saralasin

Topics: Angiotensin II; Animals; Blood Pressure; Hypertension, Malignant; Hypertension, Renal; Hyponatremia; Juxtaglomerular Apparatus; Osmolar Concentration; Pepstatins; Plasma Volume; Rats; Renin; Saralasin; Vasopressins; Water-Electrolyte Imbalance

In anaesthetized dogs that were sodium-depleted or subjected to thoracic caval constriction, Sar1-Ala8-angiotensin II produced a striking decrease in aldosterone secretion; also, arterial pressure fell while plasma renin activity (PRA) increased. Recent preliminary observations in conscious dogs during angiotensin II blockade with measurements of the plasma aldosterone level, arterial pressure and PRA have confirmed these observations; a striking fall in plasma aldosterone and arterial pressure occurred while PRA increased. In the rat, sodium depletion produced a marked increase in PRA and aldosterone secretion; studies with angiotensin II blockade during administration of the nonapeptide converting enzyme inhibitor or Sar1-Ala8-angiotensin II demonstrated an important role for angiotensin II in mediating the increase in aldosterone secretion during sodium depletion in the rat. In experimental high output failure secondary to a large aortic-caval fistula, angiotensin II blockade revealed that angiotensin II decreases renal blood flow and helps to maintain the level of arterial pressure; thus, the kidney participates in the compensatory action of angiotensin II to increase total peripheral resistance. Angiotensin II blockade in both one and two-kidney renal hypertensive dogs revealed that angiotensin II was important in the pathogenesis of the acute phase, but in chronic renal hypertension the mechanisms appeared to be angiotensin II-dependent.

Topics: Aldosterone; Angiotensin II; Animals; Blood Pressure; Dogs; Heart Failure; Hypertension, Renal; Kidney; Rats; Regional Blood Flow; Renin; Saralasin; Species Specificity; Time Factors

Topics: Aldosterone; Angiotensin II; Animals; Blood Pressure; Calcium; Dogs; Hypertension; Hypertension, Renal; Kidney; Norepinephrine; Propranolol; Rabbits; Rats; Renin; Saralasin; Sodium

1. Saralasin and converting enzyme inhibitors SQ 20881 and captopril induced increases in plasma renin activity to greater than 14 ng h-1 ml-1 in 43 out of 44 patients with untreated renovascular hypertension when studied in the seated position and on normal sodium intake. This degree of response was absent in patients with normal-renin essential hypertension and present in only three out of 26 with high-renin essential hypertension. 2. Reductions of greater than approximately 9% in diastolic pressure in response to these three drugs occurred regularly in renovascular hypertension (95%) but also frequently in high-renin (65%) and normal-renin (26%) essential hypertension. 3. Prior sodium depletion abolished the specificity of the renin and depressor responses to angiotensin blockage for renovascular hypertension. 4. Some patients with bilateral renovascular and all with malignant hypertension also exhibited these responses to angiotensin blockade that are characteristic of unilateral renovascular hypertension.

Topics: Angiotensin II; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Captopril; Clinical Enzyme Tests; Diet, Sodium-Restricted; Humans; Hypertension, Renal; Hypertension, Renovascular; Proline; Renin; Saralasin

Saralasin, a specific competitive inhibitor of angiotensin II, was administered in a controlled, prospective study designed to test the hypothesis that this agent is a useful tool for the detection of renovascular hypertension. 13 patients, 11 with renovascular hypertension and 2 with high-renin essential hypertension, showed a gross, readily apparent decrease in blood pressure after receiving saralasin. 8 patients with essential hypertension and normal or low renin levels exhibited no depressor response to the drug. In the patients with renovascular hypertension, blood pressure response during angiotensin blockade compared favourably with renal vein renin determinations as a predictor of operative results. Because saralasin testing has resulted in few if any falsely positive or negative results when considered as a diagnostic procedure for renin-mediated hypertension, and because it is safe, it may become an ideal initial screening procedure. The saralasin test (either bolus injection or sustained infusion) is completely valid only if the patient is mildly salt-depleted, is not taking other antihypertensive medication, and is genuinely hypertensive at the time of the test.

Topics: Adult; Angiotensin II; Blood Pressure; Clinical Trials as Topic; Female; Humans; Hypertension, Renal; Male; Middle Aged; Prospective Studies; Renin; Saralasin

1. In the fetal lamb, suprarenal aortic blood flow reduction is known to lead to an upper body hypertension. The dependency of this hypertension on the renin-angiotensin system was investigated. 2. Intravenous infusions of saralasin or saline vehicle were begun before suprarenal aortic blood flow reduction and continued for 24 h. 3. In those fetuses receiving saline, upper body arterial blood pressure was significantly elevated both 60 min (P < 0.05) and 24 h (P < 0.05) after blood flow reduction. In those fetuses receiving an infusion of saralasin, upper body arterial blood pressure failed to rise after 60 min of blood flow reduction. However, 24 h later, blood pressure was elevated (P < 0.05), though the increase was not as great as that seen in the saline infused fetuses (P < 0.05). 4. From these results, we conclude that the initial increase in upper body arterial blood pressure seen after suprarenal aortic blood flow reduction is dependent upon the renin-angiotensin system. However, as early as 1 day later, some other mechanism is responsible for sustaining the hypertension.

Topics: Animals; Blood Pressure; Female; Fetus; Hypertension, Renal; Infusions, Intravenous; Pregnancy; Regional Blood Flow; Renal Circulation; Renin; Renin-Angiotensin System; Saralasin; Sheep

Vascular rings from normal rabbit renal arteries, when bathed in processed plasma from 3-day renal artery stenosis (RAS) rabbits, had greater contractile responses to norepinephrine than did matched rings bathed in processed plasma from sham-operated rabbits. This vascular hyperresponsiveness of the rings produced by 3-day RAS plasma was abolished by the angiotensin II (ANG II) antagonist [Sar1, Ile8] ANG II but not by [Sar1, Ala8] ANG II at a dose that completely blocked the contractile responses of the rings to ANG II. The addition of [Sar1, Ala8]-ANG II to rings bathed in normal rabbit plasma did not alter the contractile responses to norepinephrine, indicating a lack of agonistic action by this ANG II analogue. These studies demonstrated that the ANG II receptors involved in the hormonally mediated vascular hyperresponsiveness in 3-day RAS rabbits are contained in the tissues that comprise these renal arterial rings.

Topics: 1-Sarcosine-8-Isoleucine Angiotensin II; Angiotensin II; Animals; Blood Pressure; Hypertension, Renal; In Vitro Techniques; Male; Muscle, Smooth, Vascular; Norepinephrine; Rabbits; Reference Values; Renal Artery; Renin; Saralasin

Congestive heart failure is an unusual complication of the hyperreninemia of Wilms' tumors. Cases with bilateral tumors present a difficult management problem. This is a report of the successful medical management of a child with congestive heart failure secondary to hyperreninemia from bilateral Wilms' tumor. Hypertension and hyperreninemia were extensively documented. Their etiologic relation to the congestive heart failure was supported by the patient's improved cardiac function following specific renin-angiotensin blockade. With unilateral tumors, surgical excision corrects the hypertension; however, with large bilateral tumors, excision is out of the question. A unique feature of this case is the ability to control the blood pressure with saralasin. With subsequent antitumor therapy, renin concentrations decreased proportional to tumor size, and renin angiotensin blocking therapy could be discontinued.

Topics: Antineoplastic Combined Chemotherapy Protocols; Blood Pressure; Dactinomycin; Echocardiography; Heart Failure; Humans; Hypertension, Renal; Infant; Kidney Neoplasms; Male; Neoplasms, Multiple Primary; Renin; Renin-Angiotensin System; Saralasin; Ultrasonography; Vincristine; Wilms Tumor

This study consisted of five different experiments with conscious rabbits. In experiment 1, the angiotensin II (ANG II) antagonist [Sar1-Ala8]ANG II infused iv into one-kidney rabbits with renal artery stenosis (RAS) of 3 days' duration, at a dose that blocked pressor responses to ANG II, did not decrease the exaggerated pressor responses to norepinephrine (NE). In experiment 2, captopril infused iv into one-kidney, 3-day, RAS rabbits blocked pressor hyperresponsiveness to NE, and the concurrent infusion of [Sar1-Ala8]ANG II did not reestablish pressor hyperresponsiveness, indicating that this ANG II analogue had no agonistic action to promote hyperresponsiveness to NE. In experiment 3, infusion of ANG II at a subpressor dose (6.7 pmol . min-1 . kg body wt-1) into normal rabbits resulted in pressor hyperresponsiveness to NE, which was blocked by [Sar1-Ala8]ANG II. Experiment 4 involved infusing [Sar1-Ala8]ANG II or [Sar1-Ile8]ANG II at various doses into 3-day RAS rabbits, to determine their abilities to attenuate the pressor responses to ANG II (100 ng/kg) and the pressor hyper-responses to NE (800 ng . min-1 . kg-1). [Sar1-Ile8]ANG II decreased the ANG II pressor responses at an ID50 dose of 64 +/- 5 (SEM) pmol . min-1 . kg-1 and attenuated the NE pressor hyper-response at an ID50 dose of 65 +/- 5 pmol . min-1 . kg-1; [Sar1-Ala8]ANG II diminished the ANG II pressor response at an ID50 dose of 757 +/- 247 and the NE pressor hyper-response at an ID50 dose of 10,061 +/- 944 pmol . min-1 . kg-1.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Angiotensin II; Animals; Blood Pressure; Hypertension, Renal; Male; Norepinephrine; Rabbits; Receptors, Angiotensin; Receptors, Cell Surface; Renal Artery Obstruction; Saralasin

In a multicentric prospective study should be tested clinically the effectiveness and the tolerance of an angiotensin-II-antagonist (Saralasin-IWF) developed by the Institut für Wirkstofforschung der Akademie der Wissenschaften, its position in the differential-diagnostic step programme of the arterial hypertension should be analysed and with it should be performed pathogenetic investigations for hypertension after kidney transplantation. Taking into consideration international studies our results confirm that the Saralasin test, taking into account strongly standardized methodical prerequisites, is suited to objectify a participation of the RAAS in the hypertension pathogenesis, without, however, thus making an absolutely reliable evidence concerning the etiology of hypertension. The Saralasin test may represent an important diagnostic criterion for an optimization of the therapy of "volume-resistant" hypertension under the conditions of haemodialysis and in connection with selective renin determinations it possesses a high value in the screening diagnostics of the arterial stenosis after allogenic kidney transplantation.

Topics: Blood Pressure; Diagnosis, Differential; Humans; Hypertension; Hypertension, Renal; Hypertension, Renovascular; Kidney Transplantation; Postoperative Complications; Renal Dialysis; Saralasin

To investigate the role of renal prostaglandin E2 (PGE2) in renovascular hypertension, urinary PGE2 was measured in rabbits with hypertension produced by left renal artery constriction. In the acute phase of renovascular hypertension (1 week after the constriction), urinary excretions of PGE2 and sodium were significantly increased without correlations with changes in the systemic blood pressure (delta BP). In this phase, delta BP was directly proportional to plasma renin activity and plasma aldosterone concentration (p less than 0.001). In the intermediate phase (5 weeks), delta BP lost significant correlations with plasma renin activity and plasma aldosterone concentration and had a inverse correlation with urinary sodium excretion (p less than 0.01). In the maintenance phase (10 weeks), delta BP showed inverse correlations (p less than 0.01) with both PGE2 and sodium excretions, although their excretions decreased to normal levels. In the clipped kidney, only urinary PGE2 excretion in the acute phase was significantly elevated (p less than 0.02), and both sodium and PGE2 excretions were significantly decreased (p less than 0.01) in the maintenance phase. In the nonclipped kidney, urinary PGE2 and sodium excretions were elevated in the acute and intermediate phases, but decreased to the control levels in the maintenance phase. In this phase, delta BP showed inverse correlation (p less than 0.01) with both PGE2 and sodium excretions from the nonclipped kidney. The infusion of saralasin, an angiotensin II analogue, dose dependently reduced the blood pressure in the acute phase, but showed no effect in the intermediate and maintenance phases.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aldosterone; Animals; Blood Pressure; Dinoprostone; Hypertension, Renal; Male; Prostaglandins E; Rabbits; Renin; Renin-Angiotensin System; Saralasin; Sodium

The renal nerve activity plays an essential role in the stimulation of plasma renin activity (PRA), which may be involved in the pathomechanism of neurogenic hypertension after sino-aortic denervation (SAD). Therefore, studies were conducted on unanesthetized rabbits (10 animals; 3-4 kg) after bilateral carotid sinus denervation plus section of cervical aortic nerves and the patterns of blood pressure (BP), heart rate (HR), and PRA were measured after a single injection-dosis of Saralasin (i.v., 10 micrograms/kg). After SAD the BP increased rapidly to 190 mm Hg within one week and remained at this high level (190-220 mm Hg) throughout the whole experiment (120 weeks). No change in BP of control rabbits (100-110 mm Hg) could be observed. Two weeks after SAD, the PRA showed a short elevation (approx. 25 ng) which subsequently returned to the levels of control rabbits (approx. 19 ng). Only in hypertensive rabbits Saralasin produced a short decrease of BP during both the initial and the whole chronic phases of hypertension, which was associated with a larger decrease of HR (1st to 5th min). Surprisingly, Saralasin induced a drop of HR also in the control rabbits. Our results suggest that also the normalized renin-angiotensin system is involved in the pathomechanism of sympathetic induced SAD-hypertension and probable permanently support the chronic state of hypertension by a relative "reninism".

Topics: Animals; Blood Pressure; Heart Rate; Hypertension, Renal; Kidney; Rabbits; Renin; Saralasin

Topics: Angiotensin II; Arginine Vasopressin; Blood Pressure; Calcium; Captopril; Cold Temperature; Enzyme Precursors; Humans; Hyperaldosteronism; Hypertension; Hypertension, Malignant; Hypertension, Renal; Magnesium; Natriuretic Agents; Propranolol; Renin; Renin-Angiotensin System; Saralasin; Sodium; Teprotide

The saralasin acetate test was performed in 17 hypertensive patients with renal transplants. These results were compared with 39 previously published reports of transplant patients who had been tested in the same manner. Eighty-two percent of our patients had a positive saralasin acetate test, suggesting renin-dependent hypertension. Baseline plasma renin activity (PRA) was significantly higher in patients with positive tests (6.96 +/- 1.75 v 2.88 +/- 0.53 ng/mL/hr). However, positive tests were obtained in several patients who had normoreninemia, and PRA levels did not correlate with the magnitude of vasodepressor BP response to saralasin. Transplant artery stenosis, acute rejection, and chronic rejection were the most common posttransplant complications associated with a positive test, but several patients had hypertension alone. While highly sensitive for renin-dependent hypertension posttransplantation, the test had poor specificity for identification of any one cause of posttransplant hypertension.

Topics: Blood Pressure; Follow-Up Studies; Graft Rejection; Humans; Hypertension, Renal; Kidney Transplantation; Male; Middle Aged; Postoperative Complications; Renal Artery Obstruction; Renin; Saralasin

The increase in arterial pressure and vascular resistance during acute unilateral renal artery stenosis (RSt) in conscious rats is, in part, dependent on elevated neurogenic vascular tone produced by an indirect neural interaction of angiotensin II (ANG II) with the sympathetic nervous system. The present experiments examined whether this interaction occurs within the central nervous system. Conscious rats that had been chronically instrumented with miniaturized Doppler flow probes for measurement of regional vascular resistance were subjected to a 50% reduction in unilateral renal flow with an implanted pneumatic occluder. Arterial pressure increased by 35% after 60 min of RSt. In animals in which the pressor response to intracerebroventricular (icv) ANG II had been eliminated by prior surgical interruption of the "ANG II pressor pathway" in the anterior hypothalamus, the increase in blood pressure following RSt was attenuated by 44% (P less than 0.01). In a second series, a central action of ANG II during acute renal hypertension (RH) was assessed by central ANG II receptor blockade with icv saralasin. Unlike normotensive controls, acutely RH animals responded to saralasin with significant (P less than 0.01) decreases in arterial pressure (-32%) and hindquarters (-26%) and contralateral renal (-9%) resistance. These changes were accentuated (-57% decrease in pressure) in animals made areflexic by prior sinoaortic baroreceptor denervation. Thus activation of the sympathetic nervous system during the early high-renin phase of RH depends significantly on a central action of ANG II. This mechanism may account for some 40-50% of the pressure increase following acute RSt.

Topics: Afferent Pathways; Angiotensin II; Animals; Carotid Sinus; Central Nervous System; Consciousness; Constriction, Pathologic; Hypertension, Renal; Hypothalamus; Male; Nerve Block; Pressoreceptors; Rats; Rats, Inbred Strains; Receptors, Angiotensin; Reflex; Renal Artery Obstruction; Saralasin

An angiotensin II antagonist, sarcosine-1, threonine-8 angiotensin II ( [Sar1, Thr8] A II), was infused preoperatively in 14 patients with renal artery stenosis. Postoperative graft patency was documented by renal flow scan in 13 patients. One of these required antihypertensive therapy immediately after surgery, while the other 12 had a significant BP reduction in the first postoperative week (141 +/- 3.7 to 110 +/- 1.6 mm Hg). With longer follow-up, six patients remained normotensive (group 1), while the other six had "residual hypertension" (group 2). There was no significant difference between the two groups as regards age, preoperative BP level, plasma renin activity, blood volume, or response to [Sar1, Thr8] A II. In contrast, clinical signs were most helpful in predicting response to surgery. "Cured" patients had shorter duration of hypertension (less than one year) than patients with residual hypertension, and less impairment of renal excretory function; three patients in group 2 but none in group 1 had a history of malignant hypertension. The decision to operate remains a multifactorial evaluation and cannot be based on results of any single test alone.

Topics: Adult; Angiotensin II; Blood Pressure; Blood Volume; Female; Heart Rate; Humans; Hypertension, Renal; Hypertension, Renovascular; Infusions, Parenteral; Male; Middle Aged; Preoperative Care; Prognosis; Renin; Renin-Angiotensin System; Saralasin

Topics: Diagnosis, Differential; Humans; Hypertension, Renal; Infusions, Parenteral; Saralasin

Constriction of the remaining renal artery of a uninephrectomized rat produced an increase in plasma renin level, a decrease in renal cortex renin level, an increase in blood pressure and a drinking response. Simultaneous infusion with the angiotensin II antagonist, saralasin, potentiated the rise in plasma renin level and blocked the rise in blood pressure. Drinking was only partially attenuated. Pretreatment with l-propranolol had no effect on the changes in plasma or kidney renin levels, but the increase in blood pressure was potentiated and the drinking response was attenuated. It is concluded that the pressor and drinking responses to renal artery constriction are partially mediated by the beta adrenergic nervous system.

Topics: Angiotensin II; Animals; Blood Pressure; Drinking; Female; Hypertension, Renal; Hypertension, Renovascular; Propranolol; Rats; Rats, Inbred Strains; Receptors, Adrenergic; Receptors, Adrenergic, beta; Renin; Renin-Angiotensin System; Saralasin

The antihypertensive effect of captopril and its mechanism of action were studied in patients with essential and renal hypertension. In mild essential hypertension (n = 12), during monotherapy with captopril (50 to 450 mg, 4 to 12 weeks) blood pressure was normalized in seven, improved in two and remained unchanged in three patients, plasma levels of active and acid-activatable inactive renin significantly increased and angiotensin II decreased, whereas no consistent changes in urinary kallikrein excretion occurred. In severe renal (n = 14) and essential (n = 9) hypertension, blood pressure was normalized in eight (seven with renal hypertension), improved in seven and unchanged in eight patients, when captopril (50 to 450 mg, 3 to 15 months) was added to the antihypertensive medication. In one patient with stenosis in a transplanted renal artery reversible renal failure occurred during captopril therapy possibly because of a steep initial decrease in blood pressure, although a toxic effect of the drug cannot be excluded. In another series of 12 renal and 8 essential hypertensive patients, a significant correlation between the acute effect of captopril (within 90 minutes) an saralasin on blood pressure was demonstrated (r=0.71, p less than 0.001). The change in blood pressure after either drug was significantly related to the initial plasma renin concentration. In conclusion, captopril seems to be an effective antihypertensive agent in essential and renal hypertension. Renal function should be monitored during captopril therapy. Our studies suggest that captopril decreases blood pressure by inhibiting the vasopressor action of the renin-angiotensin system.

Topics: Angiotensin II; Captopril; Electrolytes; Humans; Hypertension; Hypertension, Renal; Hypertension, Renovascular; Proline; Renin; Renin-Angiotensin System; Saralasin

Topics: Angiotensin II; Humans; Hypertension, Renal; Hypertension, Renovascular; Saralasin

This report documents a case of hypertension caused by an intrarenal arterial stenosis in a ten-year-old girl. The renovascular origin of her hypertension was suggested by a positive saralasin acetate infusion test, and the lesion was identified by use of the subtraction technique in renal arteriography. Partial nephrectomy resulted in resolution of the patient's hypertension with good function in the remaining portion of the kidney.

Topics: Angiography; Angiotensin II; Child; Female; Humans; Hypertension, Renal; Hypertension, Renovascular; Nephrectomy; Renal Artery Obstruction; Saralasin

1. Previous studies have shown that administration of converting enzyme inhibitor (CEI, SQ 20 881) to two-kidney, one-clip Goldblatt hypertensive (GH) rats clipped for 3-4 weeks resulted in marked increases in glomerular filtration rate (GFR), water and sodium excretion by the non-clipped kidneys. The clipped kidneys exhibited reduced function that was due, in part, to the reductions in arterial pressure. To evaluate further the hypothesis that the renal responses to CEI were due primarily to the inhibition of angiotensin II rather than other factors, we infused the angiotensin II competitive blocker, saralasin, into GH rats under sodium pentobarbital anaesthesia and examined renal haemodynamics and excretory function of each kidney before and during saralasin infusion and after cessation of saralasin infusion. 2. Saralasin reduced mean arterial blood pressure from 164 +/- 4 to 124 +/- 4 mmHg. Despite the profound fall of arterial pressure, significant increases in renal blood flow from 5.82 +/- 0.22 to 9.15 +/- 0.76 ml/min and glomerular filtration rate from 1.46 +/- 0.10 to 2.18 +/- 0.14 ml/min were observed in the non-clipped kidneys. Renal vascular resistance decreased from 2.34 (+/- 0.14) x 10(5) to 1.17 (+/- 0.19) x 10(5) kPa 1(-1) s [2.34 (+/- 0.14) x 10(6) to 1.17 (+/- 0.19) x 10(6) dyn s cm-5]. Also, concomitant diuresis and kaliuresis and a delayed natriuresis occurred. 3. The clipped kidneys exhibited reductions in renal blood flow, GFR and excretory function during saralasin infusion. 4. Normal rats receiving the identical dose of saralasin responded with a slight but significant decrease in arterial pressure. The increase in renal blood flow and GFR were less than those observed in the non-clipped kidneys of hypertensive rats. 5. These data provide further support to the hypothesis that an angiotensin II-mediated elevation in renal vascular resistance and impairment of renal function exist in the non-clipped kidneys of GH rats.

Topics: Angiotensin II; Animals; Blood Pressure; Glomerular Filtration Rate; Hypertension, Renal; Kidney; p-Aminohippuric Acid; Potassium; Rats; Rats, Inbred Strains; Renal Circulation; Renin-Angiotensin System; Saralasin; Sodium; Vascular Resistance

An attempt was made to produce one-clip, one-kidney hypertension in the rat with diabetes insipidus (DI). Renal artery constriction in unilaterally nephrectomized DI rats (DI-clip) resulted in an increased blood pressure in all 9 rats, but this response was only transient in 3 rats. The magnitude of the hypertension was less in the DI-clip rats than in Long-Evans rats subjected to the same protocol (LE-clip). Infusion of saralasin i.v. at doses of 10 and 30 micrograms/kg . min. 4 to 6 weeks after surgery was without effect on mean arterial pressure in LE-clip and control DI rats, but substantially lowered blood pressure in the DI-clip rats (p less that 0.05 - 0.01). It is concluded that vasopressin is not essential for the production of one-clip, one kidney hypertension in the rat, and that, in the DI rat, the renin-angiotensin system is an important factor in this form of hypertension.

Topics: Angiotensin II; Animals; Blood Pressure; Diabetes Insipidus; Disease Models, Animal; Dose-Response Relationship, Drug; Hypertension, Renal; Hypertension, Renovascular; Hypothalamic Diseases; Male; Muridae; Saralasin; Vasopressins; Water-Electrolyte Balance

During aetiological investigation of recently developed hypertension in a 31-year-old man, isolated dissection of the upper branch of the right renal artery was discovered. Injection, after sodium depletion, of saralasin, a competitive angiotensin II inhibitor, resulted in significant fall of the mean arterial pressure. During sodium depletion, the plasma renin activity was higher in the right renal artery (17.8 ng/ml/h) than in the left artery (9.4 ng/ml/h) and the infra-renal portion of the inferior vena cava (8.7 ng/ml/h). These figures suggested that surgical treatment of the dissection would have beneficial effects on blood pressure. Six months after resection of the pathological arterial segment and replacement by a graft from the internal saphenous vein, blood pressure had spontaneously returned to normal levels.

Topics: Adult; Aortic Dissection; Humans; Hypertension; Hypertension, Renal; Hypertension, Renovascular; Male; Renal Artery; Renin; Saralasin

Saralasin (Sar1, Ala8 angiotensin II), a competitive antagonist of angiotensin II, or captopril, an angiotensin-converting enzyme inhibitor, were infused for 12 hr into conscious rats with Goldblatt two-kidney one-clip hypertension at an early stage (mean interval from clipping 36 days) and a chronic stage (151 days). In the early phase infusions of either saralasin or captopril produced a significant fall in blood pressure, which was maximal at 30 min, although the majority of animals remained hypertensive. In the chronic phase, saralasin produced a small and nonsignificant fall in blood pressure, whereas captopril produced a fall similar to that observed in the early group. No further fall in blood pressure was seen over the 12 hr period. PRC was markedly elevated in the early phase but did not differ significantly from normal in the chronic phase. The blood pressure fall produced by saralasin was significantly correlated with preinfusion PRC (r = 0.72 for the early group and 0.81 for the chronic group; p less than 0.01), whereas the fall in blood pressure produced by captopril was poorly correlated with PRC (r = 0.04 and 0.14, respectively). Captopril produced a minor fall and saralasin a minor elevation of blood 3 pressure in normal animals. Infusions of dextrose without inhibitor caused no change in blood pressure. Removal of the renal artery clip normalized blood pressure in the majority (88%) of animals in either the early or chronic phases. It is concluded that 12 hr infusions of these inhibitors are no more effective than 30 min infusions and do not fully correct hypertension in this model. Furthermore, the greater vasodepressor effect of captopril compared to saralasin in chronic hypertensive animals and the lack of correlation between PRC and change in blood pressure with captopril suggest that this agent has an action independent from blockade of the renin-angiotensin system. Removal of the renal artery clip is more effective than renin-angiotensin blockade in correcting Goldblatt two-kidney one-clip hypertension.

Topics: Angiotensin II; Animals; Blood Pressure; Captopril; Female; Hypertension, Renal; Hypertension, Renovascular; Infusions, Parenteral; Proline; Rats; Renin; Saralasin; Time Factors

Topics: Angiotensin II; Humans; Hypertension, Renal; Hypertension, Renovascular; Saralasin

The diagnostic usefulness of the timed intravenous pyelogram (IVP), isotopic renal flow study (renal flow), stimulated plasma renin activity (SPRA), saralasin infusion test, and renal vein renins (RVR) in detecting possible renal vascular hypertension was studied in relation to age. Among patients who had been off medication for 2 weeks and who had normal renal X-ray findings, the percentage of those with a high SPRA dropped from 22.3% in those aged 20-29 to 4.2% in those aged 60-69 years, and that in those showing a positive saralasin test dropped from 8.3% in those aged 20-29 to 4.3% in those aged 60-69. But among those with abnormal renal X-ray findings, the percentage rose from 5.7% to 20% (high SPRA) and from 16.3% to 33% (positive saralasin test). A high SPRA or positive saralasin detected a renal abnormality in 11.7% and 50%, respectively, of patients aged 20-29, and 75% and 85.7%, respectively, of those aged 60-69. The percentage of all patients on or off medication with abnormal renal X-ray findings and a renal vein renin ratio > 1.5 increased from 14.2% among those aged 20-29 to 84.2% among those aged 60-69. The results indicate an increasing usefulness with age of a high SPRA or a positive saralasin test in indicating an abnormal renal X-ray and an abnormal renal vein renin ratio, and thus a potentially correctable lesion.

Topics: Adult; Age Factors; Aged; Angiotensin II; Female; Humans; Hypertension, Renal; Hypertension, Renovascular; Kidney; Male; Middle Aged; Radioisotope Renography; Renal Veins; Renin; Saralasin; Urography

A "bolus" dose (110 microgram) of the angiotesin II (A II)-blocker 1-Sar-8-Ala-A II (Saralasin, S) followed by its slow rate infusion (5 microgram/min/rat) for thirty min, was injected before and after the complete ganglionic blockade by pentolinium (P) in unanaesthetized unilaterally clipped renal hypertensive rats (the opposite kidney remained untouched). Pentolinium was also injected like a "bolus" dose (3 mg) followed by slow infusion (0.1 mg/min/rat) for thirty min. The observations were made until the fifth week after clipping the left renal artery. A consistent maximal hypotensive response was observed after the "bolus test" with both drugs. When S was the first drug injected, an inverse correlation was found between the percent decrease in arterial pressure (BP) by S and the percent decrease in BP by P (r = --0.83, P < 0.01, n = 8). Thus whenever a greater hypotensive effect was obtained by S, a smaller neural pressor component remained to be blocked by P. On the other hand, when P was the first drug injected a lesser A II pressor component remained to be blocked by S in the hypertensive rats. The results suggest that a considerable A II pressor effect in two-kidney renovascular hypertension is mediated via neurogenic mechanisms from the first week. A direct pressor vasoconstriction was found to be significant in cases with very high plasma-renin activity.

Topics: Angiotensin II; Animals; Blood Pressure; Ganglionic Blockers; Hypertension, Renal; Hypertension, Renovascular; Infusions, Parenteral; Male; Pentolinium Tartrate; Rats; Renin; Saralasin

The effects of an angiotensin-II analog (saralasin, i.v.) and of a converting enzyme inhibitor (captopril, oral) were compared in 12 sodium-depleted patients with hypertension. The decrease of the mean intraarterial pressure (MAP) with captopril (-21.5 +/- [SEM] 4.3 mm Hg) was more pronounced (P < 0.001) than the change of MAP during saralasin (-10.5 +/- 4.0 mm Hg). The pretreatment arterial plasma renin activity (log PRA) was closely related to the change of MAP during saralasin (r = -0.94; P < 0.001) and also to the captopril-induced change of MAP (r = -0.82; P < 0.001); similar results were obtained for the log plasma angiotensin (PA) I and II levels. The change of MAP was more pronounced, however, with captopril than during saralasin at any level of pretreatment PRA, PAI or PAII. Saralasin did not affect heart rate (P > 0.4), but during captopril the heart rate increased by 5.1 beats/min (P < 0.001). Captopril produced a 70% decrease of PAII, but the change of MAP was poorly related to the changes of PAII (r = -0.57; P < 0.05); PRA and PAI rose threefold to fourfold. PRA, PAI, and PAII all increased during saralasin. These observations may suggest that the antihypertensive action of captopril is not based solely on the inhibition of AII formation, but also the agonistic effect of saralasin has to be considered.

Topics: Adult; Angiotensin I; Angiotensin II; Blood Pressure; Captopril; Female; Heart Rate; Humans; Hypertension; Hypertension, Renal; Hypertension, Renovascular; Male; Peptidyl-Dipeptidase A; Proline; Renin; Saralasin

1. Unilateral renal artery constriction in rats maintained on a sodium-deplete, but not sodium-replete, diet induced an augmented acute vasodepressor response to kininase II inhibition produced by an intravenous injection of the dipeptidyl carboxypeptidase inhibitor captopril (250 microgram) during continuous saralasin-induced angiotensin II blockade (10 microgram/min). Dietary sodium restriction alone in sham-operated rats had no effect. 2. Acute bilateral adrenalectomy (18-24 h) did not preclude the demonstration of an augmented response to kininase II inhibition in sodium-depleted rats with benign two-kidney, one-clip hypertension. Neither did chronic administration of deoxycorticosterone acetate in intact rats elicit an augmented response. 3. The augmented acute vasodepressor response to kininase II inhibition in sodium-depleted rats with benign two-kidney, one-clip hypertension is probably due to bradykinin potentiation and secondary to an increased activity of the kallikrein-kinin system. The mechanism responsible for this apparent increase is not known, but neither hyperangiotensinemia nor hyperaldosteronism seems to play a role.

Topics: Adrenalectomy; Angiotensin-Converting Enzyme Inhibitors; Animals; Blood Pressure; Captopril; Desoxycorticosterone; Diet, Sodium-Restricted; Hypertension, Renal; Hypertension, Renovascular; Male; Rats; Saralasin

Topics: Angiotensin-Converting Enzyme Inhibitors; Angiotensins; Animals; Blood Pressure; Bradykinin; Captopril; Dogs; Humans; Hypertension, Renal; Kallikreins; Kidney; Kinins; Proline; Renin; Saralasin

1. Removal of the renal artery constriction but not of the clipped kidney restored the blood pressure to normal levels in Goldblatt two-kidney rats with hypertension of more than 4 months' duration. 2. Despite the differences in blood pressure response, both surgical procedures lowered plasma renin concentration to normal or below normal values. 3. Administration of the oral converting enzyme inhibitor SQ 14 225 produced a marked fall in blood pressure in Goldblatt kidney rats with chronic hypertension. However, a prolonged infusion of the angiotensin II antagonist saralasin was quite ineffective. The difference in response to the two inhibitors may have been due to bradykinin potentiation by the converting enzyme inhibitor. 4. Although plasma renin is often elevated in Goldblatt two-kidney rats with hypertension of more than 4 months' duration, the renin-angiotensin system plays no role in the maintenance of blood pressure at this stage.

Topics: Angiotensin II; Animals; Blood Pressure; Captopril; Chronic Disease; Female; Hypertension, Renal; Hypertension, Renovascular; Nephrectomy; Proline; Rats; Renin; Saralasin

The usefulness of screening patients for renovascular hypertension by infusion of saralasin, a competitive antagonist of angiotensin II, was evaluated. Responses were compared in 19 patients with proved renovascular hypertension and in 34 without renovascular hypertension, as indicated by renal arteriography and renal venous renin studies. Saralasin infusion was carried out in the morning after furosemide, 80 mg by mouth, had been given the previous evening. Seventy-five percent of patients with and 12 percent of those without renovascular hypertension had a reduction in diastolic pressure of 5 mm Hg or more during saralasin infusion; only 45 percent of patients with and 6 percent of those without renovascular hypertension had a reduction of 10 mm Hg or greater during infusion. In comparison, 80 percent of patients with and 18 percent of those without renovascular hypertension had a positive intravenous pyelogram. The predictive value of a positive saralasin test (5 mm Hg or greater reduction in diastolic pressure) was calculated for varying prevalence rates of renovascular hypertension with use of Bayes theorem. The results indicate that when the prevalence rate of renovascular hypertension among hypertensive patients is 5 percent only 25 percent of positive saralasin tests will correctly predict its presence.

Topics: Adolescent; Adult; Aged; Angiotensin II; Arteriosclerosis; Blood Pressure; Child; Female; Fibromuscular Dysplasia; Humans; Hypertension, Renal; Hypertension, Renovascular; Male; Middle Aged; Renal Artery Obstruction; Renin; Saralasin; Urography

A positive saralasin test in patients with angiographic evidence of renovascular disease and other positive functional tests gives further assurance that these patients will achieve normal or substantially reduced blood pressure postoperatively. In our experience with proved renovascular hypertension there was a 19 per cent incidence of falsely negative saralasin tests. Therefore, saralasin should not be used as the sole screening test in hypertensive patients suspected of having surgically correctable lesions. There is a direct correlation between elevated renin activity and a positive saralasin test. In some patients saralasin may be more sensitive than any other currently used test to detect overactivity of the renin-angiotensin system. This would determine those patients with technical errors in renin sampling and assays. Of the 16 patients (all normotensive) who had 6-month followup tests 5 had elevated peripheral renin activity, probably owing to furosemide stimulation. Of these 5 patients 2 had a positive postoperative saralasin test, raising the question of potential falsely positive responses in cases of essential hypertension and coincidental non-functional renal artery stenosis. Patients with high renin essential hypertension may respond to saralasin, even in the absence of renal artery lesions. A saralasin test should be done in a hospital where all specific conditions can be met and potential complications handled promptly.

Topics: Adolescent; Adult; Aged; Angiotensin II; Blood Pressure; Child; False Negative Reactions; Female; Humans; Hypertension, Renal; Hypertension, Renovascular; Kidney; Kidney Function Tests; Male; Middle Aged; Prognosis; Prospective Studies; Renin; Saralasin

Topics: Adolescent; Adult; Aldosterone; Angiotensin II; Blood Pressure; Female; Heart Rate; Humans; Hypertension; Hypertension, Renal; Hypertension, Renovascular; Male; Middle Aged; Renin; Saralasin; Sodium

The effect of an intravenous infusion of saralasin in a rising dosage on blood pressure, central haemodynamics, forearm blood flow and venous distensibility was tested in 11 subjects with chronic non-uraemic renal disease. Only 1 subject had an elevated resting plasma renin activity, and in him saralasin produced a drop in systolic and diastolic blood pressures due to a decrease of the total peripheral vascular resistance whereas the plasma renin activity markedly rose. Among the remaining 10 subjects, whose plasma renin activity was within the normotensive range, blood pressure rose transiently in 3, with the lowest dose of aralasin, due to an increase in the total peripheral vascular resistance. Both these parameters returned to the control level when continuing the infusion and increasing its dosage. Excluding this initial period from the analysis, no relevant change, even with a more than tenfold increase in the saralasin dosage and a duration of the infusion of 1 h, was found in the following: blood pressure, cardiac and stroke index, heart rate, total peripheral vascular resistance, central and peripheral venous pressures, forearm blood flow and vascular resistance, forearm blood volume and venous distensibility. The haemodynamic response to the Valsalva manoeuvre remained unaffected by saralasin. It is concluded that angiotensin plays an active role in changing the haemodynamics and in elevating the blood pressure in subjects with chronic non-uraemic renal disease only in those cases where plasma renin activity is raised.

Topics: Adult; Angiotensin II; Blood Pressure; Chronic Disease; Female; Forearm; Heart Rate; Humans; Hypertension, Renal; Kidney Diseases; Male; Middle Aged; Regional Blood Flow; Renin; Saralasin; Vascular Resistance

In two-kidney Goldblatt hypertensive, spontaneously hypertensive, and normotensive control rats, the activity of the renin-angiotensin system was tested during variation of sodium balance. Acute, exactly calculable and selective changes in total body sodium were achieved by haemodialysing conscious rats, using dialysates with high and low sodium contents. The activity of the renin-angiotensin system was evaluated by blood pressure response to angiogtensin II blockade (saralasin bolus injection; 25 micrograms/kg b.w., i.v.) and plasma renin activity. During sodium-depletion, blood pressure maintenance became renin-dependent; sodium-loading caused a decrease of renin-angiotensin activity in renovascular hypertension. A weak direct correlation between depressor response to saralasin and the plasma renin activity could be established in the different sodium-depleted and sodium-loaded states.

Topics: Animals; Blood Pressure; Disease Models, Animal; Hypertension; Hypertension, Renal; Hypertension, Renovascular; Male; Rats; Renal Dialysis; Renin; Saralasin; Sodium

The number of studies in the literature on diagnostic and therapeutic uses of angiotensin antagonists has been increasing geometrically. Nearly 1,000 publishsd items deal with saralasin alone, although neither saralasin nor captopril is yet approved for general use or widely available. Reports to date represent only a fraction of the eventual situations in which these agents are likely to help the researcher and clinician. Food and Drug Administration approval of both agents is pending, and both are expected to be available soon. Consequently, the practitioner will want to become familiar with their usefulness, especially to screen for secondary forms of hypertension and to treat moderate to severe primary or secondary hypertension.

Topics: Angiotensin II; Angiotensins; Blood Pressure; Captopril; Diagnosis, Differential; Humans; Hypertension; Hypertension, Renal; Hypertension, Renovascular; Proline; Renin; Saralasin

Current methods to evaluate renovascular hypertension in the pediatric population often requires a general anesthetic. Saralasin, an angiotensin II competitive inhibitor, is a safe, noninvasive technique which can be utilized at the bedside in a salt-depleted child off antihypertensive medication. Two illustrative cases are presented.

Topics: Aldosterone; Angiotensin II; Blood Pressure; Child; Humans; Hypertension, Renal; Hypertension, Renovascular; Infusions, Parenteral; Male; Radiography; Renal Artery; Renin; Saralasin

Topics: Adolescent; Adult; Aged; Angiotensin II; Blood Pressure; Chemical Phenomena; Chemistry; Female; Humans; Hypertension; Hypertension, Renal; Male; Middle Aged; Renin; Saralasin

Renal vein catheterization was performed in fifteen hypertensive patients with unilateral renal disease. Samples for measurement of plasma renin concentration were obtained from each of the two renal veins and from the femoral artery (or the inferior caval vein)-before and during saralasin infusion. Saralasin infusion induced a significant decrease in blood pressure. In ten patients with lateralization of renin secretion before infusion, saralasin induced a 2-fold increase of the renin gradient across the diseased kidney, whereas there was no significant renin gradient across the contralateral kidney neither before nor after saralasin infusion. Thus, the renal venous renin ratio (diseased/contralateral) increased from a mean value of 2.10 to 4.13. In five patients without lateralization of renin secretion prior to infusion, saralasin induced a significant increase of renin gradient across both kidneys. In consequence, evidence for lateralization did not emerge and the renal vein renin ratio remained unchanged at 1.10. In cases with lateralization of renin secretion, the use of saralasin provides confirmatory evidence for strictly unilateral renin secretion with suppression of renin output from the contralateral kidney. In patients without obvious lateralization of renin secretion before saralasin, the administration of this angiotensin II inhibitor can serve to demonstrate a potential renin for renin secretion, shared by both kidneys.

Topics: Angiotensin II; Blood Pressure; Catheterization; Humans; Hypertension, Renal; Renal Veins; Renin; Saralasin

Most series report a significant percentage of nondepressor (negative) responses to saralasin infusions in patients with surgically curable renovascular hypertension. Usually the infusions have been performed with the supine position. In the present study saralasin infusions were done in 33 acutely sodium-depleted hypertensive patients--17 with renovascular and 16 with the essential variety. Most patients were infused in the seated and supine positions to test the hypothesis that there might be a higher incidence of positive (vasodepressor) responses to the saralasin infusion when patients are in a sitting position. The results did, in fact, show a larger number of positive responses to saralasin in the seated patients with renovascular hypertension than in those in the supine position (88% versus 71%). There was a modest increase in the rate of false-positive responses in the patients with essential hypertension who were infused in the seated position (31% versus 23%). However, inasmuch as the saralasin infusion test is proposed as a screening procedure for renovascular hypertension, some false-positive responses are acceptable.

Topics: Angiotensin II; False Positive Reactions; Humans; Hypertension, Renal; Hypertension, Renovascular; Posture; Saralasin

Renal hemodynamics following administration of the angiotensin II antagonist Saralasin were studied in untouched kidney of 11 two-kidney hypertensive rats and in kidneys of 7 control rats using an electromagnetic flowmeter. Renal blood flow (RBF) in controls averaged 6.2 +/- (SD) 1.7 vs. 5.2 +/- 0.9 ml/min/g kidney weight in the hypertensive group (n.s.). Renal vascular resistance (RVR) was significantly increased in untouched kidneys: 2.6 +/- 0.5 vs. 1.8 +/- 0.4 dyn . sec . cm-5 . 10(6) . g kidney weight-1. Following Saralasin infusion mean arterial blood pressure decreased significantly more in hypertensive rats. RBF increased by 24% in untouched kidneys vs. 12% in controls (p < 0.05), indicating a 34% decrease of RVR in hypertensive rats vs. 18% (p < 0.005) in controls. These results indicate that the increased RVR in untouched kidneys is highly dependent on circulating angiotensin II, which may reduce the antihypertensive role of the untouched kidney.

Topics: Angiotensin II; Animals; Blood Pressure; Hemodynamics; Hypertension, Renal; Kidney; Male; Rats; Regional Blood Flow; Saralasin; Vascular Resistance

1. In the conscious normotensive and two-kidney Goldblatt hypertensive dog a transient agonist response to the intravenous infusion of saralasin (1 microgram min-1 kg-1)was manifested by a small increase in blood pressure (6-12) mmHg) and 28-30% increase in renal vascular resistance. 2. These increases in blood pressure and renal vascular resistance were unaffected by administration of either phentolamine or guanethidine. 3. The agonist response in the conscious dog is most likely accounted for by a direct action of saralasin on vascular angiotensin receptors.

Topics: Adrenergic alpha-Agonists; Angiotensin II; Animals; Blood Flow Velocity; Blood Pressure; Dogs; Female; Guanethidine; Hypertension, Renal; Kidney; Male; Phentolamine; Renin; Saralasin; Vascular Resistance

The response of arterial pressure to an infusion of saralasin was compared to the effect of surgical correction of renal vascular lesions (3 to 6 months after surgery) in eleven patients whose hypertension was associated with uni or bilateral stenosis of renal artery. Saralasin was infused after four days of dietary sodium restriction (10-40 mEq/day). An excellent correlation (r = 0.83, p less than 0.005) between the effects of saralasin and surgery was obtained. There was no correlation between the response to saralasin or to surgery and the ratio of renal vein renin activities. It is suggested that saralasin may be a good tool for predicting the effect of surgery in renovascular hypertension, when infused in moderately sodium depleted patients.

Topics: Adult; Angiotensin II; Blood Pressure; Diet, Sodium-Restricted; Female; Humans; Hypertension, Renal; Hypertension, Renovascular; Male; Middle Aged; Prognosis; Renin; Saralasin

1 Prolonged infusion (11 h) of both saralasin and angiotensin-converting enzyme inhibitor (SQ20881) gradually lowered BP in two-kidney hypertensive rats to levels similar to that in normotensive rats infused with dextrose. 2 Saralasin did not lower BP in DOCA-salt hypertensive rats. 3 These observations support the notion that in chronic renal hypertension, angiotensin II may maintain hypertension by a slowly developing action. 4 Plasma angiotensin II in rats infused with SQ20881 was suppressed relative to renin, but was not eliminated. 5 Chromatography of angiotensin II extracts from dogs infused with converting enzyme inhibitor (SQ14,225) showed that the very high levels of angiotensin I achieved after treatment with SQ14,225 can lead to falsely high estimated angiotensin II levels as a result of angiotensin I cross-reacting with the angiotensin II assay.

Topics: Angiotensin I; Angiotensin II; Angiotensin III; Angiotensin-Converting Enzyme Inhibitors; Animals; Blood Pressure; Disease Models, Animal; Dogs; Female; Hypertension, Renal; Male; Oligopeptides; Proline; Rats; Saralasin; Teprotide

Topics: Adult; Angiotensin II; Female; Humans; Hypertension, Renal; Hypertension, Renovascular; Male; Middle Aged; Saralasin

Topics: Aldosterone; Angiotensin II; Animals; Humans; Hypertension; Hypertension, Renal; Renin; Saralasin

Topics: Adolescent; Adult; Aged; Angiotensin II; Binding, Competitive; Blood Pressure; Dose-Response Relationship, Drug; Female; Humans; Hypertension; Hypertension, Malignant; Hypertension, Renal; Male; Middle Aged; Natriuresis; Posture; Renin; Saralasin; Sodium; Time Factors; Vasoconstriction

Topics: Adolescent; Adult; Aged; Angiotensin II; Blood Pressure; False Negative Reactions; Female; Furosemide; Humans; Hypertension, Renal; Male; Methods; Middle Aged; Posture; Propranolol; Renal Artery Obstruction; Renin; Saralasin; Sodium Chloride

Topics: Adolescent; Angiotensin II; Blood Pressure; Child; Child, Preschool; Diagnosis, Differential; Evaluation Studies as Topic; Female; Humans; Hypertension; Hypertension, Renal; Hypertension, Renovascular; Infusions, Parenteral; Male; Methods; Nephrectomy; Renin; Saralasin

Topics: Adult; Angiotensin II; Blood Pressure; Blood Volume; Female; Humans; Hypertension, Renal; Hypertension, Renovascular; Infusions, Parenteral; Kidney Failure, Chronic; Male; Middle Aged; Nephrectomy; Renal Dialysis; Renin; Saralasin

Topics: Adult; Blood Pressure; Endarterectomy; Evaluation Studies as Topic; Female; Humans; Hypertension, Renal; Hypertension, Renovascular; Infusions, Parenteral; Kidney; Male; Middle Aged; Radiography; Recurrence; Renal Artery Obstruction; Renin; Saralasin; Sodium

Topics: Captopril; Humans; Hypertension, Renal; Hypertension, Renovascular; Male; Middle Aged; Saralasin; Teprotide

Topics: Angiography; Captopril; Evaluation Studies as Topic; Humans; Hypertension, Renal; Hypertension, Renovascular; Kidney; Radioisotope Renography; Renal Artery; Renin; Saralasin; Teprotide

Topics: Angiotensin II; Animals; Blood Pressure; Hypertension, Renal; Hypertension, Renovascular; Male; Rabbits; Renin; Saralasin; Time Factors

Topics: Adult; Angiotensin II; Female; Humans; Hypertension, Renal; Hypertension, Renovascular; Male; Middle Aged; Renin; Saralasin

Topics: Adolescent; Adult; Angiotensin II; Blood Pressure; Dose-Response Relationship, Drug; Humans; Hypertension; Hypertension, Renal; Middle Aged; Renin; Saralasin; Sodium

The saralasin test was performed in 68 hypertensives. A clear-cut dependence of the test results on initial plasma-renin concentration and particular sodium balance was demonstrated. Because of this dependence the saralasin test should be performed only under constant conditions. A mild stimulation of the renin-angiotension system by salt restriction to a mean sodium excretion of 50 mmol daily and 80 mg furosemide by mouth 12 hours before the test seems best. In this way essential and renovascular hypertension could be distinguished with considerable reliability (P less than 0.001). Among patients with essential hypertension one could clearly separate those with high plasma-renin concentration from those with a normal or low one. Among patients with renovascular hypertension those with haemodynamically significant renal artery stenosis could with high probability be distinguished from those with non-effective stenosis. A positive saralasin test without testing the function of the normal contralateral kidney does not provide an indication for operation.

Topics: Adult; Aged; Angiotensin II; Diagnosis, Differential; Furosemide; Humans; Hypertension; Hypertension, Renal; Middle Aged; Renin; Saralasin

Baseline plasma renin activity and responses to saralasin and converting enzyme inhibitor SQ 20881 (teprotide) in 47 untreated patients with surgically correctable renovascular hypertension were compared to those in 100 patients with high- and normal-renin essential hypertension. All 32 renovascular patients on normal sodium intake had high renin-sodium profiles and renin values greater than or equal to 5 ng angiotensin I/mL.h, as compared to 20 of 64 with essential hypertension. Diagnostic discrimination was greatly enhanced by infusion of saralasin or SQ 20881, which elicited marked reactive hyperreninemia in 31 of 32 renovascular patients but in only two of 64 with essential hypertension. Reactive hyperreninemia appeared to be more a specific test for renovascular hypertension than depressor responses. Prior dietary sodium depletion abolished this specificity. The results suggest that after initial screening with renin measurements, testing with angiotensin blocking agents may be a useful secondary screening procedure for more invasive and definitive procedures.

Topics: Angiotensin II; Blood Pressure; Diagnosis, Differential; Diastole; Diet; Evaluation Studies as Topic; Humans; Hypertension, Renal; Hypertension, Renovascular; Infusions, Parenteral; Injections, Intravenous; Natriuresis; Oligopeptides; Renin; Saralasin; Sodium; Teprotide; Time Factors

Blood pressure responses to the infusion of saralasin and plasma renin levels were measured in 31 hypertensive patients following preparation with frusemide. Five patients had unilateral renal artery stenosis, with renal vein ratios lateralising strongly to the affected side. Saralasin produced depressor responses in 3 of these but failed to evoke significant effects in the other 2, despite the fact that in both cases hypertension was subsequently alleviated by renal bypass surgery. A further period of more severe sodium depletion increased plasma renin levels and the depressor effect of saralasin, but did not help to differentiate renal artery stenosis from other forms of hypertension.

Topics: Adult; Angiography; Angiotensin II; Blood Pressure; Diagnosis, Differential; False Negative Reactions; Female; Humans; Hypertension, Renal; Hypertension, Renovascular; Male; Middle Aged; Renal Artery Obstruction; Renin; Saralasin; Sodium

Topics: Abdominal Neoplasms; Angiotensin II; Blood Pressure; Child; Humans; Hypertension, Renal; Hypertension, Renovascular; Male; Nephrectomy; Pheochromocytoma; Saralasin; Vasopressins

1. Pentolinium tartrate (a ganglionic blocker) was injected in conscious rats during the early and late phases of two-kidney renal hypertension produced by aortic ligation. 2. In the early phase ( 5 days after aortic ligation), ganglionic blockade resulted in a decrease in blood pressure equal to that obtained in normotensive rats. Later, at days 12 and 40, for equally severe hypertension, ganglion blockade resulted in a greater decrease in blood pressure. 3. A 30 min infusion of [Sar1, Ala8]angiotensin II during the pentolinium-induced nadir in blood pressure resulted in a further decrease in blood pressure at day 5. Later, at days 12 and 40, this effect was smaller. 4. A 300 min infusion of [Sar1, Ala8]angiotensin II normalized the blood pressure in hypertensive rats at day 40. This delay response may be secondary to a central effect of the antagonist, reducing neurogenic tone or peripheral antagonism of locally generated angiotensin II in the blood vessel walls. 5. At day 40, removal of the small left kidney resulted in a greater decrease in blood pressure. This suggests the presence of a renal factor other than renin in the chronic phase of this hypertension.

Topics: Angiotensin II; Animals; Blood Pressure; Hypertension, Renal; Male; Nerve Tissue; Pentolinium Tartrate; Rats; Renin; Saralasin

To facilitate the identification of patients with renal vascular hypertension, we evaluated four potential screening tests: rapid-sequence urography, systolic-diastolic abdominal bruit, upright plasma renin activity (PRA), and response to saralasin infusion. Our study included 379 normal subjects, 199 essential hypertensive patients with normal renal angiograms, and 64 patients with surgically responsive renal vascular hypertension. Thirty-nine percent of patients with renal vascular hypertension had systolic-diastolic bruits, 76% abnormal urograms, and 27% a PRA greater than 30 ng of angiotensin 1/mL.3 h. Only one half of the 23 patients with renal vascular hypertension tested had a depressor response to saralasin, as did two of 13 essential hypertensive patients. In essential hypertensive subjects, 1% had systolic-diastolic bruits, 2% abnormal urograms, and 5% upright renin values greater than 30 ng of angiotensin 1/mL.3 h. The screening combination of urogram, bruit, or upright renin value offered a test sensitivity of 93%, with a specificity of 92%. The results of saralasin infusion failed to increase the diagnostic yield.

Topics: Abdomen; Adolescent; Adult; Aged; Auscultation; Child; Child, Preschool; Clinical Enzyme Tests; Female; Humans; Hypertension, Renal; Hypertension, Renovascular; Male; Methods; Middle Aged; Renal Artery; Renin; Saralasin; Urography

Topics: Adult; Angiotensin II; Blood Pressure; Cardiac Output; Female; Humans; Hypertension, Renal; Male; Middle Aged; Renin; Saralasin; Sodium; Vascular Resistance

Topics: Angiotensin II; Animals; Glomerular Filtration Rate; Hemodynamics; Hydrostatic Pressure; Hypertension, Renal; Male; Microcirculation; Nephrons; Rats; Renin; Saralasin; Vascular Resistance

In two-kidney Goldblatt hypertensive, spontaneously hypertensive, and normotensive control rats the activity of the renin-angiotensin system was tested during variation of sodium balance. Acute, exactly calculable and selective changes of total body sodium were achieved by hemodialyzing the conscious rats using dialysate with either high or low sodium content. The activity of the RAS was evaluated by blood pressure response to AT II blockade (saralasin bolus injection; 25 micrograms/kg b.w., i.v.) and the plasma-renin activity. During sodium depletion blood pressure maintenance became renin-dependent; sodium loading caused a decrease of renin-angiotensin activity in renovascular hypertension. A weak direct correlation between deprssor response to saralasin and the PRA could be established in the different sodium-depleted and -loaded states.

Topics: Angiotensin II; Animals; Blood Pressure; Hypertension, Renal; Hypertension, Renovascular; Male; Rats; Rats, Inbred Strains; Renal Dialysis; Renin; Saralasin; Sodium; Time Factors

A positive saralasin test in patients with angiographic evidence of renovascular disease and other positive functional tests gives further assurance that these patients will achieve normal or substantially reduced blood pressure postoperatively. In our experience with proved renovascular hypertension there was a 19% incidence of falsely negative saralasin tests. Therefore, saralasin should not be used as the sole screening test in hypertensive patients suspected of having surgically correctable lesions. There is a direct correlation between elevated renin activity and a positive saralasin test. In some patients saralasin may be more sensitive than any other currently used test to detect overactivity of the renin-angiotensin system. This would determine those patients with technical errors in renin sampling and assays. Of the 16 patients (all normotensive) who had 6-month followup tests 5 had elevated peripheral renin activity, probably owing to furosemide stimulation. Of these 5 patients 2 had a positive postoperative saralasin test, raising the question of potential falsely positive responses in cases of essential hypertension and coincidental non-functional renal artery stenosis. Patients with high renin essential hypertension may respond to saralasin, even in the absence of renal artery lesions. A saralasin test should be done in a hospital where all specific conditions can be met and potential complications handled promptly.

Topics: Adult; Aged; Angiotensin II; Child; Endarterectomy; Female; Humans; Hypertension, Renal; Hypertension, Renovascular; Kidney; Male; Middle Aged; Nephrectomy; Saralasin; Spleen

In patients with unilateral vascular kidney disease and hypertension, ratio of renal-vein-renin was compared with 131I-Hippuric-acid clearance and change in blood pressure during Saralasininfusion. The ratio of renal-vein-renin was positively correlated with the ratio in renal plasma flow between the kidneys in all patients studied. The ratio of renins therefore is a result of two factors: The difference in renin secretion and the difference in blood flow in the two kidneys. In patients with angiotensin independent hypertension renin-ratios up to 2.0 were found without relevance to elevated blood pressure. When the difference in renal blood flow between both kidneys was small, even a slight difference in renal vein renin indicated hypertension related to increased renin secretion. Renin-ratios in the critical range between 1.5 and 2.5 should only be interpreted in respect to a similar ratio in renal blood flow.

Topics: Adult; Aged; Blood Pressure; Female; Hippurates; Humans; Hypertension, Renal; Iodine Radioisotopes; Kidney; Male; Metabolic Clearance Rate; Middle Aged; Regional Blood Flow; Renin; Saralasin

The "effective" contribution of angiotensin II in blood pressure regulation was investigated in 6 patients on maintenance hemodialysis who were hypertensive at the time of the study (MAP 133 +/- 5 mmHg). Saralasin, a specific angiotensin II inhibitor, was infused at 0.5 and 2.5 microgram/kg/mn three hours before andone hour after hemodialysis. Before hemodialysis, a mean arterial pressure decrease of 13.2 to 19 p. 100 was obtained in 5 patients, arterial pressure being normalized in three of them. After hemodialysis, saralasin induced a normalization of arterial pressure in these 5 subjects. One patient, who was resistant to the saralasin infusion before and after the hemodialysis procedure, can be considered as purely volume-dependent. The renin-angiotensin system is probably one of the primary determinant of dialysis-resistant hypertension. However, a negative response to saralasin should encourage to control hypertension by more vigorous ultrafiltration during dialysis.

Topics: Adult; Angiotensin II; Female; Humans; Hypertension, Renal; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis; Saralasin

Topics: Angiotensin II; Blood Pressure; Diagnosis, Differential; Diastole; Humans; Hypertension; Hypertension, Renal; Hypertension, Renovascular; Renin; Saralasin

1. Plasma renin activity, response to saralasin and exchangeable sodium have been measured in 43 patients with early renal disease. 2. Blood pressure was directly proportional to plasma renin activity. However, mean plasma renin activity was lower in patients with renal disease than in normal controls. 3. Blood pressure fell in response to saralasin infusion in proportion to the pre-infusion plasma renin activity. 4. Exchangeable sodium in hypertensive patients with renal disease did not exceed that in normotensive patients in contrast to earlier reports. Discrepancies may arise from the difficulty in interpreting measured exchangeable sodium in relation to body build.

Topics: Adolescent; Adult; Aged; Blood Pressure; Female; Humans; Hypertension, Renal; Male; Middle Aged; Renin; Saralasin; Sodium

Topics: Angiotensin II; Humans; Hypertension, Renal; Hypertension, Renovascular; Renal Veins; Renin; Saralasin

Topics: Acute Disease; Angiotensin II; Animals; Chronic Disease; Hypertension, Renal; Male; Rats; Renin; Saralasin

Topics: Adult; Aldosterone; Angiotensin II; Blood Pressure; Female; Furosemide; Humans; Hypertension; Hypertension, Renal; Male; Middle Aged; Potassium; Renin; Saralasin; Sodium

The effect of total adrenalectomy on the mechanisms of arterial pressure control was studied in uninephrectomized rats with and without renal artery stenosis (Goldblatt one-kidney model). Four groups of rats were prepared and maintained on high-salt intake (1% NaCl): uninephrectomized-KI; KI + adrenalectomy-KIAx; uninephrectomized with renal artery stenosis-GI; and GI with adrenalectomy-GIAx. Over 3 wk blood pressure rose significantly in both GI and GIAx but the degree of increase in GI was greater. Hyponatremia, hyperkalemia, and increased plasma urea nitrogen were observed in both KIAx and GIAx. Plasma renin concentration (PRC) and plasma renine activity (PRA) were markedly increased and plasma renin substrate (PRS) was decreased in both adrenalectomized groups. Infusion of saralasin resulted in significant and similar reductions in mean arterial pressure (MAP) in KIAx and GIAx, but had no effect on MAP in KI and GI. These results allow approximations of the contribution to total MAP of identifiable components, which are: the total adrenal component, the renin-angiotensin system component, which partially compensates for loss of the adrenal secretions, and the independent effect of the renal artery clip. Thus, a multifactorial analysis of GI hypertension is provided.

Topics: Adrenal Glands; Adrenalectomy; Angiotensin II; Animals; Blood Pressure; Blood Urea Nitrogen; Body Weight; Heart; Hypertension, Renal; Male; Nephrectomy; Organ Size; Potassium; Rats; Renal Artery Obstruction; Renin; Saralasin; Sodium

Topics: Angiotensin II; Humans; Hypertension; Hypertension, Renal; Saralasin

Topics: Angiotensin II; Animals; Blood Pressure; Bradykinin; Diet, Sodium-Restricted; Drug Synergism; Enzyme Inhibitors; Female; Hypertension, Renal; Male; Nephrectomy; Rats; Renin; Saralasin; Vasoconstrictor Agents

Topics: Angiotensin II; Animals; Blood Pressure; Disease Models, Animal; Dogs; Hypertension, Renal; Nephrectomy; Renin; Saralasin

We have studied the effects of intravenous infusion of saralasin, a competitive antagonist of angiotensin II, in 27 hypertensive patients: 13 had essential hypertension, 14 had renal lesions which involved the renal artery in 9 cases. In essential hypertensives saralasin administration did not significantly lower blood pressure, even after mild salt depletion. It induced a decrease in blood pressure in 7 patients with renal abnormalities (5 with renal artery stenosis, 2 with unilateral parenchymal disease). It may be suggested that in these cases hypertension was dependent, at least partly, on the renin-angiotensin system. In agreement with other investigators, we have found a relationship between the level of plasma renin activity and the blood pressure decrease obtained by saralasin. In patients with unilateral renal artery stenosis, blood pressure decrease was related to renal vein ratio of plasma renin activity.

Topics: Adult; Angiotensin II; Female; Humans; Hypertension; Hypertension, Renal; Male; Middle Aged; Renal Artery Obstruction; Renin; Saralasin

The angiotensin II (AII) antagonist [Sar1-Ala8]AII (Saralasin) was injected into the brain ventricles (IVT) and intravenously (IV) in five different types of hypertensive unanesthetized rats. Renal hypertension was studied 16-22 days after kidney clipping. Intravenous infusions of cumulative doses (0.1-100 microgram/kg per min) and IVT injections (5-40 microgram) of Saralasin did not change mean arterial pressure (MAP) in controls and in one-clip, one-kidney Goldblatt hypertension, whereas MAP decreased in one-clip, two-kidney Goldblatt hypertension following IV and IVT Saralasin. In two-clip, two kidney hypertensive rats, IVT Saralasin decreased MAP but was ineffective when infused IV. Both IV and IVT Saralasin increased MAP in DOC hypertension. In spontaneously hypertensive (SH) rats, IV Saralasin increased MAP; IVT injection decreased MAP. The effect of IVT Saralasin in SH rats persisted 15-20 h after nephrectomy. We conclude that plasma AII may contribute to peripheral and central mechanisms of blood pressure regulation. The dissociation of the effects of IV and IVT Saralasin and the persistance of blood pressure decrease in nephrectomized SH rats following IVT Saralasin further support a role for locally formed brain angiotensin.

Topics: Angiotensin II; Animals; Blood Pressure; Desoxycorticosterone; Female; Hypertension; Hypertension, Renal; Injections, Intravenous; Injections, Intraventricular; Male; Rats; Renin; Saralasin

1. Sar1-Ala8-Angiotensin II (an angiotensin antagonist) was infused in rats during the development and maintenance of renal hypertension produced by aortic ligation between renal arteries. 2. In the early phase (5 and 12 days after ligation), infusion of the antagonist markedly decreased blood pressure although it did not reach normal pressures. Later (day 40) only a modest decrease in blood pressure was noted. 3. Removal of the small left kidney always decreased the blood pressure to normal pressures. 4. It is concluded that the renin-angiotensin system is the major pressor component in the initiation of this hypertension. Later, other factors of renal origin assume a pressor function.

Topics: Angiotensin II; Animals; Blood Pressure; Hypertension, Renal; Male; Nephrectomy; Rats; Renin; Saralasin

Topics: Adolescent; Angiotensin II; Blood Pressure; Humans; Hypertension, Renal; Male; Renin; Saralasin

The effect of saralasin, a competitive inhibitor of angiotensin II, was assessed in hypertensive patients with unilateral renal artery stenosis after furosemide application. A significant fall of systemic arterial blood pressure, an increase of renal venous renin activity, significantly on the stenosed side in patients without arteriosclerosis of the contralateral kidney, and an almost equal decrement of renal blood flow in both kidneys were observed. Conceivably saralasin exerts different sodium-dependent effects on peripheral angiotensin II and specific intrarenal vascular receptors.

Topics: Angiotensin II; Arteriosclerosis; Blood Pressure; Female; Humans; Hypertension, Renal; Hypertension, Renovascular; Kidney; Male; Regional Blood Flow; Renal Artery; Renal Artery Obstruction; Renal Veins; Renin; Saralasin

Topics: Adolescent; Adult; Aldosterone; Angiotensin II; Blood Pressure; Female; Humans; Hypertension; Hypertension, Renal; Kidney; Male; Middle Aged; Receptors, Angiotensin; Renal Artery Obstruction; Renin; Saralasin

In 34 patients saralasin was infused after variable degrees of sodium depletion in order to differentiate between essential and renin-induced hypertension. After sodium-depletion of short duration mean arterial pressure dropped more than 10 mm Hg in 9 of 25 patients with essential and in 7 of 9 patients with renin-induced hypertension. After long-lasting sodium depletion the fall of mean arterial pressure exceeded 10 mm Hg in 11 of 16 patients with essential and in 8 of 9 patients with renin-induced hypertension. Thus saralasin did not discriminate essential and renin-induced hypertension. Also, plasma renin concentration before and after saralasin did not allow to differentiate between the two forms of hypertension. The changes of renin during infusion of saralasin was negatively correlated to the change of blood pressure. Renal vein renin ratio in patients with renovascular hypertension was not modified by saralasin. Renin and aldosterone changed inversely during saralasin infusion.

Topics: Aldosterone; Angiotensin II; Blood Pressure; Humans; Hypertension; Hypertension, Renal; Renin; Saralasin

The mechanisms involved in residual or recurrent hypertension following operation to correct renal artery stenosis were studied in 10 patients by performing angiotensin II blockade with Saralasin (Sarcosine, alanine, angiotensin II) before and after operation. Peripheral renin and renal vein renin determinations, angiography, and renography were done as well. The limitations of renin determinations are cited and the application of angiotensin II blockade as a specific method of detecting renin-dependent hypertension before and after operation are presented. Saralasin infusion under the controlled conditions of our study proved to be a sensitive method for detection of renin-dependent hypertension. The results of Saralasin infusion correlated closely with peripheral and renal vein renin determinations. Thus angiotensin II blockade before and after operation may supercede more invasive and less specific diagnostic methods.

Topics: Angiotensin II; Humans; Hypertension, Renal; Hypertension, Renovascular; Radiography; Recurrence; Renin; Saralasin

Topics: Adult; Child; Female; Humans; Hypertension, Renal; Hypertension, Renovascular; Male; Middle Aged; Radiography; Radioisotope Renography; Renal Artery; Saralasin

A modification of the infusion test with saralasin, an angiotensin II antagonist for the detection of renin-dependent high blood pressure was studied in renal hypertensive rats and in normotensive and hypertensive subjects. Infusion was started at a rate of 0.01 microgram/kg x min saralasin and the dose was increased ten-fold at 15 min intervals. A significant fall of diastolic blood pressure was observed at the dose of 0.1 microgram/kg x min in renal hypertensive rats, in healthy subjects treated with diuretics, and in patients with renovascular hypertension (saralasin responders). Plasma concentrations of angiotensin I, angiotensin II and of saralasin as well as plasma renin activity were measured. At the lowest infusion rate of 0.01 microgram/kg x min, saralasin plasma levels were 40-fold higher than plasma angiotensin II levels. The decrease in arterial blood pressure occurred at lower doses of saralasin than the increase of plasma renin due to inhibition of feedback on the renin secreting cells. It is concluded that if the saralasin test is performed by a stepwise increase of the infusion rate, potentially dangerous complications such as hypo- or hypertensive reactions can be avoided. The diagnostic reliability is improved by such a procedure since false positive and false negative responses may be prevented. The pressor effect of saralasin in non-renin dependent patients is an advantage since it causes a more marked difference of blood pressure change between saralasin responders and non-responders.

Topics: Angiotensin I; Angiotensin II; Animals; Blood Pressure; Chlorthalidone; Diet, Sodium-Restricted; Female; Humans; Hypertension, Renal; Kinetics; Male; Rats; Renin; Saralasin

The response of arterial pressure to an infusion of saralasin was compared to the effect of surgical correction of renal vascular lesions (3 to 6 months after surgery) in eleven patients whose hypertension was associated with uni or bilateral stenosis of renal artery. Saralasin was infused after four days of dietary sodium restriction (10--40 mEq/day). An excellent correlation (r = 0.83, p less than 0.005) between the effects of saralasin and surgery was obtained. There was no correlation between the response to saralasin or to surgery and the ratio of renal vein renin activities. It is suggested that saralasin may be a good tool for predicting the effect of surgery in renovascular hypertension, when infused in moderately sodium depleted patients.

Topics: Adult; Angiotensin II; Blood Pressure; Diet, Sodium-Restricted; Female; Humans; Hypertension, Renal; Hypertension, Renovascular; Male; Middle Aged; Saralasin

Normal human plasma contains an active form of renin that is activated by acidification to pH 3.0 and comprises 56% of the total renin. In our study, inactive renin was also present in plasma from five anephric persons, and the proportion of active to inactive renin in these subjects was similar to normal. Plasma from normal pregnant women contained increased concentrations of inactive renin and the proportion of inactive renin was raised to around 66%. Plasma from persons with renal hypertension contained varying amounts of inactive renin but the mean percentage (35%) was lower than normal. An infusion of saralasin sufficient to lower the blood pressure in five subjects with renal hypertension resulted in a rise in active renin concentration but no change in the concentration of inactive renin. Plasma angiotensin II correlated with active renin but not with inactive renin, suggesting that the inactive renin does not produce angiotensin II in vivo.

Topics: Angiotensin II; Angiotensinogen; Animals; Blood Pressure; Cattle; Diet; Enzyme Activation; Female; Freezing; Humans; Hydrogen-Ion Concentration; Hypertension, Renal; Male; Pregnancy; Renin; Saralasin; Sodium

In two hypertensive patients with renal-artery stenosis, overactivity of the renin-angiotensin system was ruled out by investigations of renin and aldosterone concentrations and by the lack of a vasodepressor response to angiotensin blockade with saralasin. Nevertheless, hypertension was cured by renal revascularisation. The date suggest that there is a form of renovascular hypertension which is not mediated by the renin-angiotensin system.

Topics: Adult; Aldosterone; Blood Pressure; Female; Humans; Hypertension, Renal; Kidney Transplantation; Middle Aged; Posture; Renal Artery Obstruction; Renin; Saralasin; Syndrome; Transplantation, Autologous

Arteriography in two patients with renovascular hypertension suggested fibromuscular hyperplasia, mainly affecting the right renal artery. When saralasin was infused intravenously there was no fall in blood-pressure in either patient. However, both had a raised renal-vein plasma-renin activity on the affected side, relative to the unaffected kidney. Auto-transplantation resulted in a sustained reduction in arterial pressure in both patients. A negative saralasin test should not necessarily exclude further investigation of young patients with severe hypertension.

Topics: Adult; Angiography; Angiotensin II; Blood Pressure; Blood Pressure Determination; Evaluation Studies as Topic; Female; Humans; Hyperplasia; Hypertension, Renal; Kidney; Kidney Transplantation; Male; Prognosis; Renal Artery; Renal Veins; Renin; Saralasin; Transplantation, Autologous

Topics: Hypertension, Renal; Renal Artery Obstruction; Renin; Saralasin

A patient with intractable congestive cardiac failure secondary to renovascular hypertension and severe coronary artery disease was infused with the competitive antagonist of angiotensin II, saralasin acetate. The infusion produced an impressive increase in cardiac output and left ventricular stroke work index in parallel with a striking decrease in the systemic and pulmonary vascular resistance, the coronary resistance, and the myocardial oxygen consumption. It is suggested that angiotensin inhibition may present advantages over other forms of treatment of congestive cardiac failure in selected cases.

Topics: Angiotensin II; Cardiac Output; Cardiac Volume; Coronary Circulation; Heart Failure; Humans; Hypertension, Renal; Male; Middle Aged; Oxygen Consumption; Pulmonary Circulation; Renin; Saralasin; Vascular Resistance

Topics: Animals; Aorta, Abdominal; Aortic Coarctation; Blood Pressure; Disease Models, Animal; Dogs; Humans; Hypertension, Renal; Infant; Nephrectomy; Radiography; Renin; Saralasin

Topics: Aldosterone; Angiotensin II; Animals; Corticosterone; Desoxycorticosterone; Extracellular Space; Hypertension; Hypertension, Renal; Hyponatremia; Rats; Renal Artery Obstruction; Renin; Saralasin; Sodium; Sodium Chloride; Teprotide

Topics: Angiotensin II; Animals; Desoxycorticosterone; Femoral Vein; Hypertension; Hypertension, Renal; Injections, Intravenous; Injections, Intraventricular; Rats; Rats, Inbred Strains; Saralasin

Topics: Angiotensin II; Blood Pressure; Humans; Hyperplasia; Hypertension, Renal; Kidney; Kidney Diseases; Regional Blood Flow; Renal Artery Obstruction; Renal Veins; Renin; Saralasin

Topics: Aldosterone; Angiotensin II; Blood Pressure; Cardiac Output; Diet, Sodium-Restricted; Heart Rate; Hemodynamics; Humans; Hypertension; Hypertension, Renal; Renin; Saralasin

Topics: Angiotensin II; Bartter Syndrome; Diagnosis, Differential; Humans; Hypertension; Hypertension, Renal; Renin; Saralasin

Angiotensin II blockade with sarcosine 1-alanine 8-angiotensin II (saralasin, P-113) was done in 40 studies of 20 hypertensive patients. Eleven of 12 patients with a depressor response to angiotensin II blockade had significant renovascular or renal disease, and nine of 10 had renal vein renin measurements that lateralized to the abnormal kidney. In contrast, none of the patients without a depressor response had renovascular abnormalities. Plasma renin activity was usually high in responders to saralasin (18 ng/ml-h) when compared with nonresponders (0.5 ng/ml-h). In these studies a correlation between the fall in blood pressure and the rise in plasma renin activity during angiotensin II blockade was observed while renin was unchanged in the absence of depressor responses. In two renovascular renin-dependent hypertensive patients, treatment with diuretics induced severe hyperreninemia and a rise in blood pressure that was reversed by sodium loading.

Topics: Angiotensin II; Blood Pressure; Furosemide; Humans; Hypertension, Renal; Renin; Saralasin; Sodium

Topics: Antihypertensive Agents; Body Water; Clonidine; Diazoxide; Ethacrynic Acid; Furosemide; Guanethidine; Humans; Hypertension, Renal; Kidney Failure, Chronic; Methyldopa; Renal Dialysis; Renin; Reserpine; Saralasin; Teprotide; Vasodilator Agents

1. In the early phase of hypertension produced by renal artery constriction with the opposite kidney intact, infusion of the angiotensin antagonist Sar1-Ala8-angiotensin II or bilateral nephrectomy lowered blood pressure. However, the extent of the fall was variable and some animals remained hypertensive after each procedure. 2. To assess whether sodium retention was the additional factor which maintained blood pressure when the renin-angiotensin system was suppressed, rats were maintained on a low-salt diet before and during the development of hypertension. The blood pressure-lowering effect of bilateral nephrectomy or antagonist infusion was not enhanced. 3. Infusion of antagonist or converting-enzyme inhibitor 6 h after bilateral nephrectomy had only a minor blood pressure-lowering action, indicating that, at this late stage after nephrectomy, the renin-angiotensin system makes only a very small contribution to blood pressure maintenance.

Topics: Angiotensin II; Animals; Blood Pressure; Female; Hypertension, Renal; Nephrectomy; Rats; Renin; Saralasin; Sodium

We found increased levels of catecholamines in some patients who had high-renin hypertension. To study relations between angiotensin and the sympathetic nerves further, we infused saralasin, a blocker of angiotensin II, into 11 hypertensive patients being evaluated for renovascular hypertension. There were variable responses of mean arterial pressure, plasma renin activity, and norepinephrine levels. When high-renin hypertensive patients with increased levels of norepinephrine were compared with those having high renin and normal levels of norepinephrine, they showed a lesser decrease in mean arterial pressure--5 +/- 5% versus 14 +/- 4%, P less than 0.05--a decrease in plasma renin activity of 20 +/- 17% versus an increase of 77 +/- 24% (P less than 0.01), and a decrease in norepinephrine levels of 42 +/- 7% versus an increase of 10 +/- 23% (P less than 0.05) (means +/- SE). The evidence suggests that patients with high-renin levels are heterogeneous and that the primary mediator of the hypertension is sympathetic tone hyperactivity in those with increased levels of norepinephrine and angiotensin excess in those with normal levels of norepinephrine.

Topics: Adolescent; Adult; Angiotensin II; Blood Pressure; Female; Humans; Hypertension, Renal; Male; Middle Aged; Norepinephrine; Renin; Saralasin; Stimulation, Chemical; Sympathetic Nervous System

Topics: Angiotensin II; Humans; Hypertension, Renal; Saralasin

Topics: Angiotensin II; Animals; Cardiac Output; Cellophane; Hemodynamics; Hypertension, Renal; Male; Perinephritis; Rabbits; Renin; Saralasin

The role of renin was assessed in moderate and severe one-clip, two-kidney hypertension in rabbits during normal and high Na intake. Severe hypertension occurred with high levels of plasma renin and creatinine and with extracellular volume depletion. In this group, hypertension was significantly reduced by the 1-hour intravenous infusion of 1,000 ng/kg of an angiotensin II antagonist or by correcting the volume depletion with a high Na intake, which also decreased renin activity and creatinine. The infusion of the antagonist after a high salt diet failed to decrease blood pressure further. Moderate hypertension occurred with plasma levels of renin that were slightly below normal and with no significant abnormalities in extracellular volume depletion or creatinine. In this group, the administration of an angiotensin II antagonist or a high salt diet did not affect any of the three parameters. In normotensive controls, the blood pressure level was not affected by either the angiotensin II antagonist or the high salt diet, despite a reduction in plasma renin activity. Thus, high levels of renin are important in maintaining severe hypertension, and these increased levels probably are accompanied by a concomitant depletion of extracellular volume. Correction of the extracellular volume depletion by a high salt diet is followed by a decrease in renin activity and in blood pressure. In contrast, renin activity does not seem to be important in maintaining moderate hypertension, the pathogenetic mechanism of which remains to be elucidated.

Topics: Angiotensin II; Animals; Blood Pressure; Creatinine; Diet; Extracellular Space; Hematocrit; Hypertension, Renal; Potassium; Rabbits; Renal Artery Obstruction; Renin; Saralasin; Sodium

Changes in plasma renin activity (PRA) and sodium balance were studied in hypertensive rabbits and dogs with one renal artery constricted and the other kidney intact (two-kidney hypertension); aldosterone secretion was measured also in the chronic hypertensive rabbits. Both PRA and aldosterone secretion were normal in some chronic hypertensive rabbits but elevated in others. Sodium balance studies revealed that some severely hypertensive rabbits with elevated PRA were in spontaneous negative sodium balance. Unlike the rabbit, PRA was never increased in the chronic hypertensive dog and sodium balance was normal. Infusion of [Sar1, Ala8]angiotensin II (P-113) decreased arterial pressure and aldosterone secretion in those hypertensive rabbits with elevated PRA but not in those rabbits with normal PRA; P-113 also did not decrease arterial pressure in the chronic hypertensive dog unless sodium depletion was superimposed. In the conscious two-kidney dog, acute renal artery stenosis increased both arterial pressure and PRA within minutes, and P-113 blocked the rise in pressure associated with the increase in PRA. Therefore, although apparent species differences between the rabbit and the dog occur, the present data indicate that neither increased PRA nor excess salt retention is essential to the chronic maintenance of two-kidney hypertension in these two species; however, in the dog a role for angiotensin II in the acute phase is indicated.

Topics: Adrenal Cortex Hormones; Angiotensin II; Animals; Blood Pressure; Blood Urea Nitrogen; Disease Models, Animal; Dogs; Female; Hypertension, Renal; Male; Methods; Potassium; Rabbits; Renal Artery Obstruction; Renin; Saralasin; Sodium

A recently developed 1-day screening procedure for angiotensinogenic ("high-renin") hypertension is based on (A) a fall in blood pressure in response to intravenous infusion of the angiotensin antagonist, saralasin (P-113), and (B) peripheral venous renin assays by radioimmunoassay, in a sodium-depleted state. Out of 700 hypertensive patients screened by these tests, 160 had renal imaging performed with technetium-99m glucoheptonate and iodine-131 Hippuran. The P-113 infusion test proved superior to peripheral venous renin assays for the detection of angiotensinogenic hypertension. Positive infusion tests correlated well with renal vein renin assays. Frequently, however, both these tests were positive with bilateral renal disease and/or malignant hypertension. While renal imaging proved valuable in indicating which patients had a unilateral abnormality, it frequently could not distinguish unilateral renovascular disease from unilateral parenchymal disease unrelated to angiotensinogenic hypertension. Twenty-five patients in this series had arteriographic renal artery stenosis, of whom 3 had false negative P-113 infusion tests, 9 had negative peripheral renin assays, and 3 had no imaging abnormalities. This study indicates that scintigraphy is a useful procedure for the investigation of hypertensive patients when the initial P-113 infusion test is positive, or discordant with other findings. By imaging, angiotensinogenic hypertension due to bilateral renal disease can be distinguished from unilateral renovascular disease, and the site of the ischemic renal tissue can usually be identified.

Topics: Adult; Angiotensin II; Humans; Hypertension, Renal; Iodine Radioisotopes; Iodohippuric Acid; Male; Middle Aged; Radiography; Radionuclide Imaging; Renal Artery Obstruction; Renin; Saralasin; Sugar Acids; Technetium

Saralasin, an angiotensin II antagonist, was infused into 49 patients with renal artery stenosis, 10 patients with essential hypertension and normal renal arteriograms, and five patients with "low-renin essential hypertension." Renal venous renin and differential renal function studies were used to assess the functional significance of arterial stenoses. "Response" to saralasin, evidenced by a fall in blood pressure during infusion, occurred in no patients with "low renin" hypertension and in only 20% of patients with normal renal arteriograms. In contrast, saralasin "response" occurred in more than 80% of patients with renal artery stenosis and lateralizing functional studies and 100% of cases of "proven" renovascular hypertension (cure or improvement of hypertension after operative treatment). We suggest that saralasin infusion might be a valuable screening test for the recognition of renovascular hypertension.

Topics: Angiotensin II; Blood Pressure; Diagnosis, Differential; Humans; Hypertension; Hypertension, Renal; Nephrectomy; Renal Artery Obstruction; Renin; Saralasin

Topics: Angiotensin II; Animals; Blood Pressure; Body Weight; Dose-Response Relationship, Drug; Female; Furosemide; Hypertension; Hypertension, Renal; Rats; Rats, Inbred Strains; Renin; Saralasin; Species Specificity

Saralasin (1-sar-8-ala-angiotensin II), a competitive inhibitor of angiotensin II, was administered to 32 patients with renovascular or essential hypertension before (Day 1) and after (Day 2) they were mildly sodium depleted by furosemide (1 mg/kg body weight). A blood pressure lowering effect of saralasin was observed in 16 of 17 patients with renovascular hypertension on Day 2, but in only 10 of the 17 on Day 1. Of the 15 patients with essential hypertension, only the four with high renin levels exhibited a vasodepressor response on Day 2; three responded similarly on Day 1. The Average net sodium loss between the 2 days was greater for patients who responded to the drug on Day 2 (170 meq) than those who did not (129 meq) (P less than 0.05); however, there was no correlation between blood pressure response and either net sodium loss or urinary sodium excretion at the time of testing. Plasma renin activity correlated with saralasin responses (r=-0.74, P less than 0.01). Saralasin testing during a state of modest sodium depletion compares favorably with renin measurements in the detection of renin-mediated hypertension.

Topics: Adult; Angiotensin II; Female; Humans; Hypertension; Hypertension, Renal; Male; Middle Aged; Prospective Studies; Renin; Saralasin; Sodium; Vasomotor System

The reliability of the angiotensin II (AT II)-antagonist Saralasin in the diagnosis of AT II-dependent forms of hypertension was investigated in 61 cases of hypertension of different etiology. In 14 patients, lowering of blood pressure by Saralasin suggested an AT II-dependent hypertension which could be ascertained in 8 patients (5 had undergone successful surgery) by increased levels of plasma-renin-activity (PRA), AT II, PRA-ratio in renal vein blood and by angiography. Besides, depressor reactions by Saralasin yielded additional information in three patients with renovascular hypertension but normal levels of PRA and AT II, in two patients with high renin essential hypertension and one patient with pheochromocytoma. This test seems to be valuable in the diagnosis of renin-dependent hypertension.

Topics: Angiotensin II; Blood Pressure; Diagnosis, Differential; Evaluation Studies as Topic; Female; Humans; Hypertension; Hypertension, Renal; Male; Renin; Saralasin

Topics: Angiotensin II; Animals; Blood Pressure; Body Fluids; Cardiac Output; Diet, Sodium-Restricted; Hypertension, Renal; Male; Rabbits; Renin; Saralasin; Sodium; Vascular Resistance

In 7 hypertensive patients with renal artery stenosis and in 1 patient with hypertension and unilateral pyelonephritic nephrophthisi the influence of the angiotensin II antagonist, saralasin on systemic hemodynamics was studied. In the patients with normal renin infusion of saralasin produced an increase in total peripheral resistance, in patients with elevated renin a decrease in peripheral resistance was observed. In 3 patients who had extremely high renin levels while under sodium saralasin produced a dangerous drop in blood pressure concomitant with a marked decrease in cardiac output and in central venous pressure, heart rate remained unchanged or increased just slightly. The findings suggest that in patients with high plasma renin peripheral resistance, venous tone, venous retrun, and cardiac output are to a large extent controlled by circulating angiotensin II.

Topics: Adult; Angiotensin II; Blood Pressure; Diet, Sodium-Restricted; Hemodynamics; Humans; Hypertension, Renal; Middle Aged; Renal Artery Obstruction; Renin; Saralasin; Vascular Resistance

Topics: Angiotensin II; Humans; Hypertension, Renal; Renal Artery Obstruction; Renin; Saralasin

Topics: Angiotensin II; Hemodynamics; Humans; Hypertension, Renal; Hypotension; Infusions, Parenteral; Male; Middle Aged; Saralasin

Renal hypertension of the two-kidney type is divided into three stages. In the first, hypertension results from the vasoconstrictor effect of angiotensin II. This persists to some extent in the second phase but there is in addition a slow-developing pressor effect, also resulting from angiotensin II and probably attributable to sodium. In the first two phases removal of the abnormal kidney corrects the hypertension. This fails in the third phase because changes in the opposite kidney maintain hypertension. Renin and angiotensin are probably not involved at this stage.

Topics: Angiotensin II; Animals; Blood Pressure; Dogs; Female; Humans; Hypertension, Renal; Kidney; Models, Biological; Nephrectomy; Renal Artery; Renal Artery Obstruction; Renin; Saralasin; Sodium; Thrombosis; Vasoconstrictor Agents

This study was designed to examine more closely the differences in blood pressure responses in hypertensive patients to two agents which block the renin-angiotensin system. Accordingly, 39 seated patients received under the same conditions both saralasin, an octapeptide competitive antagonist of angiotensin II, and the nonapeptide converting enzyme inhibitor, SQ20881, which blocks the generation of angiotensin II from angiotensin I. A second component of the study involved administration of these agents in 10 addtional studies in anephric subjects. Although both agents produced maximal responses in blood pressure that correlated well with each other (p less than 0.001) and with the pretreatment plasma renin levels (p less than 0.001), analysis of the results by renin subgroups revealed significant differences. Thus, both drugs lowered the diastolic pressures of patients with high renin levels, but but converting enzyme inhibitor produced changes of greater amplitude (p less than 0.05). In contrast, saralasin was consistently pressor in both patients with low renin levels and anephric patients in whom converting enzyme blockade preduced no significant changes in blood pressure. Another impressive disparity in the responses to the two agents occurred in the group with normal renin levels in whom saralasin produced either neutral or pressor responses (mean change was +2.0 +/- 1.5 standard error of the mean (SEM) per cent control diastolic pressure) whereas the converting enzyme inhibitor consistently induced depressor responses (mean change was -10.2 +/- 1.2 per cent, p less than 0.001). Altogether, the results suggest that converting enzyme inhibitor tests for angiotensin II-dependent blood pressure with more sensitivity than the partial agonist saralasin. Moreover, it is unlikely that the differences between the responses to the two agents were due to bradykinin accumulation, since depressor responses to converting enzyme inhibitor were not observed in the patients with low renin levels and the anephric patients.

Topics: Adolescent; Adult; Angiotensin II; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Female; Humans; Hypertension; Hypertension, Renal; Kidney Diseases; Male; Middle Aged; Oligopeptides; Renin; Saralasin; Sodium; Teprotide

Cellophane perinephritis hypertension was produced in four dogs, while five additional dogs served as normotensive controls. A competitive antagonist of angiotensin II, 1-sarcosine-8-alanine angiotensin II, was infused iv into these conscious dogs at a rate of 6 mug/min/kg of body weight for 45 min. Arterial pressure averaged 170 +/- 11 (SEM) mm Hg in the dogs with perinephritic hypertension, and was not altered significantly during infusion of the angiotensin antagonist. In the normal dogs the arterial pressure averaged 100 +/- 10 mm Hg and likewise, did not change during administration of the angiotensin analog. Plasma renin activity values were essentially the same in these two groups of dogs and did not change during infusion of the angiotensin antagonist. These studies provide strong evidence that the renin-angiotensin system is not involved in maintaining the elevated arterial pressure in dogs with chronic hypertension produced by cellophane perinephritis.

Topics: Angiotensin II; Animals; Blood Pressure; Dogs; Female; Hypertension, Renal; Renin; Saralasin

Unilateral renal artery plication in dogs reduced renal blood flow by 80% and produced a sustained elevation in arterial pressure whereas plasma renin activity increased for only 4 days. Sodium was retained for 3 days after plication, but this response is similar to that after a sham operation. Of seven dogs studied chronically, elevated arterial pressure was sustained for 27 days or longer in six animals. In three dogs hypertension continued for 2 mo before collateral vessels developed and arterial pressure fell; ligation of these collaterals restored hypertension. Arterial pressure was unaffected by an infusion of [1-sarcosine, 8-alanine] angiotensin II in chronic hypertensive dogs on a normal sodium intake. This angiotensin antagonist lowered arterial pressure after sodium depletion, but became ineffective following rapid sodium repletion. Chronic hypertensive dogs showed normal responses to deoxycorticosterone acetate. These findings suggest that the renin-angiotensin system is not critically involved in maintenace of chronic two-kidney renovascular hypertension in the dog. The data also show that the homeostatic role played by the renin-angiotensin system in the maintenance of arterial pressure remained intact in chronic hypertension.

Topics: Angiotensin II; Animals; Blood Pressure; Corticosterone; Dogs; Female; Heart Rate; Hypertension, Renal; Renin; Saralasin; Sodium

One hundred sixteen patients underwent operation for renovascular hypertension from 1962 through 1975; 64% had aortorenal reconstruction and 36% had nephrectomy. Sixty-six percent were cured and 19% were improved. Rapid sequence intravenous pyelography, radioisotope renography, and renal arteriography were equal in ability to detect renovascular hypertension. Bilateral renal biopsy specimens had excellent prognostic value when performed in a graded semiquantitative manner. Plasma renin activity was the most consistently useful criterion for prediction of surgical cure if the following requirements were used: (1) elevated peripheral plasma renin activity, (2) elevated renin from the affected kidney, and (3) suppressed renin secretion from the contralateral kidney. An angiotensin II antagonist, saralasin acetate, used in six patients before operation in an attempt to identify those whose hypertension depended on angiotensin II activity, produced a depressor response correlating well with the surgical result.

Topics: Adolescent; Adult; Aged; Angiotensin II; Biopsy; Child; Female; Humans; Hypertension, Renal; Kidney; Male; Middle Aged; Radioisotope Renography; Renal Artery; Renal Artery Obstruction; Renal Veins; Renin; Retrospective Studies; Saralasin; Urography

Topics: Adult; Angiotensin II; Female; Humans; Hypertension, Renal; Hypotension; Renin; Saralasin; Sodium

The angiotensin antagonist saralasin (1-sar-8-ala-angiotensin II) was given to 27 patients with different forms of secondary hypertension. The blood pressure fell in 6 of 7 patients with renal artery stenosis and in 4 of 10 patients with terminal renal failure on regular hemodialysis. No change or a rise in blood pressure was observed in 3 patients with Cushing's syndrome, 4 patients with primary aldosteronism, 3 patients with hypertension and a unilateral small kidney of other than renovascular origin, and 6 patients with terminal renal failure. It can be concluded from the results that angiotensin II is involved in the pathogenesis of renovascular hypertension and in some cases of hypertension accompanying chronic renal failure.

Topics: Angiotensin II; Cushing Syndrome; Humans; Hyperaldosteronism; Hypertension, Renal; Kidney Failure, Chronic; Renal Artery Obstruction; Saralasin

Specific antagonists of the renin angiotensin system have been used to investigate the role of this hormonal system in blood pressure homeostasis and in different types of experimental and clinical hypertension. Using this approach it was possible to show that renin via angiotensin participates actively in blood pressure maintenace, particularly following sodium depletion. Such antagonists, if available for oral administration and taken together with a diuretic, would be useful therapeutically.

Topics: Adult; Angiotensin II; Animals; Humans; Hypertension; Hypertension, Renal; Male; Oligopeptides; Rats; Renin; Saralasin; Sodium; Teprotide

Sar1-Ala8-angiotensin II was infused intravenously (10 mug/kg/min) in 14 patients with renovascular hypertension, including 11 with renal artery stenosis. Brachial artery pressure and heart rate remained unchanged in six patients who were on a daily sodium intake of 130 mEq. In 12 tests performed after sodium depletion, the decrease in mean arterial pressure ranged from 13 to 76 mm Hg and showed a significant correlation with the plasma renin concentration prevailing immediately before the infusion of the drug (r = 0.81; p less than 0.001). The hypotensive response was due to a drop in total peripheral resistance. Heart rate and cardiac output showed slight increases 10 min after the start of saralasin infusion.

Topics: Adult; Angiotensin II; Blood Pressure; Female; Heart Rate; Hemodynamics; Humans; Hypertension, Renal; Male; Middle Aged; Renin; Saralasin; Sodium; Time Factors

Topics: Angiotensin II; Animals; Blood Pressure; Humans; Hypertension, Renal; Renal Artery Obstruction; Renin; Saralasin; Sodium; Time Factors

Athough in general, measurement of renal vein renin appears to give a good prediction as to the subsequent response to surgery, its main value lies in its ability to reflect changes in renal plasma flow; true changes in renin secretion rate being much more difficult to detect. Although it is a little early to say how much information can be derived from saralasin infusions, caution must be exercised in necessarily assuming that the test accurately reflects subsequent surgical response.

Topics: Adult; Aldosterone; Angiotensin II; Blood Pressure; Child; Female; Humans; Hypertension, Renal; Male; Prognosis; Renin; Saralasin

Topics: Adrenal Glands; Aldosterone; Angiotensin II; Animals; Aorta; Colon; Heart; Hemodynamics; Humans; Hypertension, Renal; In Vitro Techniques; Lung; Renin; Saralasin; Stomach; Thirst

Topics: Angiotensin II; Blood Pressure; Humans; Hypertension; Hypertension, Renal; Saralasin

Angiotensin blockade was established in hypertensive patients with the competitive inhibitor saralasin and the blood pressure response was compared to prior renin determinations. Two patients with subsequently confirmed renovascular hypertension had normal peripheral renin and non-lateralizing renal vein renin ratios, yet both showed a clear-cut lowering of blood pressure after administration of the blocking agent, indicating the presence of renin-mediated hypertension. Thus, direct in vivo testing with saralasin appears to offer certain advantages over renin determinations.

Topics: Angiotensin II; Blood Pressure; Female; Humans; Hypertension, Renal; Hypertension, Renovascular; Male; Middle Aged; Radiography; Renal Artery Obstruction; Renal Veins; Renin; Renin-Angiotensin System; Saralasin

Topics: Angiotensin II; Animals; Blood Pressure; Furosemide; Hypertension, Renal; Male; Rats; Renal Artery Obstruction; Renin; Saralasin

The angiotensin antagonist saralasin was given intravenously to six normotensive students before and after dietary sodium restriction and to two patients with renovascular hypertension. Both patients responded to the angiotensin antagonist with a decrease of the systolic (32 and 38 mm Hg) and of the diastolic (29 and 16 mm Hg) blood pressure. The small changes in blood pressure observed in the normotensive subjects during the infusion of the angiotensin antagonist indicate that angiotensin II plays no important role in the control of normal blood pressure in recumbent men. The fall in blood pressure induced by saralasin in both patients, however, demonstrates that their hypertension was at least partly angiotensin-dependent. Renal vein renin determination led to the same conclusions. The saralasin infusion test seems to be a simple procedure to diagnose angiotensin-dependent hypertension and will probably help to identify patients with suspected renovascular hypertension.

Topics: Adult; Angiotensin II; Blood Pressure; Diet, Sodium-Restricted; Female; Humans; Hypertension, Renal; Injections, Intravenous; Male; Renal Veins; Renin; Saralasin; Time Factors

Topics: Angiotensin II; Humans; Hypertension, Renal; Saralasin

Topics: Antihypertensive Agents; Diuretics; Furosemide; Humans; Hypertension; Hypertension, Renal; Physical Exertion; Posture; Potassium; Renin; Saralasin; Water-Electrolyte Balance

Topics: Adolescent; Adult; Angiotensin II; Aorta, Thoracic; Aortic Coarctation; Blood Pressure; Humans; Hypertension, Renal; Male; Middle Aged; Renin; Saralasin; Sodium

The angiotensin-blocking agent, saralasin, was given by rapid intravenous (bolus) injection to 21 hypertensive patients. A marked depressor response (average blood-pressure decrease of 30 mm Hg systolic and 20 mm Hg diastolic at 10 minutes after injection) was noted in 13 patients, of whom 11 had renovascular hypertension and 2 had high-renin essential hypertension. No change from prebolus blood-pressure was apparent at 10 minutes in 8 control patients with essential hypertension and normal or low peripheral plasma-renin activity. In all patients, blood-pressure response to saralasin bolus (10 mg) correlated with blood-pressure response to subsequent infusion of saralasin (10 microgram/kg/min). Blood-pressure response to rapid intravenous injection of saralasin--the "saralasin bolus test"--has many characteristics of an ideal screening procedure for renin-mediated hypertension.

Topics: Adult; Angiotensin II; Blood Pressure; Humans; Hypertension; Hypertension, Renal; Injections, Intravenous; Renin; Saralasin; Time Factors

Topics: Aldosterone; Aminoglutethimide; Angiotensin II; Animals; Dehydroepiandrosterone; Humans; Hypertension; Hypertension, Renal; Mineralocorticoids; Natriuresis; Norepinephrine; Patient Compliance; Phenoxybenzamine; Renal Artery Obstruction; Renin; Saralasin; Spironolactone

Topics: Angiotensin II; Blood Pressure; Hypertension, Renal; Oligopeptides; Saralasin; Teprotide

An angiotensin II inhibitor was administered to rats with two-kidney Goldblatt hypertension. The inhibitor produced a marked drop in blood pressure after 5 weeks but no significant change after 15 weeks of hypertension. However, even after 15 weeks of hypertension, following sodium depletion by either diuretics or a low sodium diet, the animals again became renin dependent as readministration of the inhibitor induced a significant fall in blood pressure. The data indicate that two-kidney Goldblatt hypertension is initially renin dependent but subsequently becomes sodium volume dependent in a way similar, although more protracted, to that already described for one-kidney Goldblatt hypertension.

Topics: Angiotensin II; Animals; Blood Pressure; Depression, Chemical; Disease Models, Animal; Hypertension, Renal; Male; Rats; Renal Artery Obstruction; Renin; Saralasin; Sodium

Topics: Angiotensin II; Animals; Hypertension, Renal; Male; Rats; Renal Artery; Renin; Saralasin; Time Factors; Urea

Twenty-four conscious male Wistar rats with hypertension induced by left renal artery clipping (two-kidney hypertension) were infused intravenously with 1-Sar-8-Ala-angiotensin II a competitive angiotensin II antagonist. The spectrum of responses was wide, ranging from a mild elevation in blood pressure to a marked fall in blood pressure, despite effective and specific angiotensin blockade in all cases. The change in blood pressure during 1-Sar-8-Ala-AII infusion activity showed a significant correlation with the level of plasma renin prevailing immediately before the infusion (r = - 0.78, P less than 0.01) but not with the prevailing blood urea level (r = 0.27, 0.1 greater than P greater than 0.05), the drgree of hypertension (r = 0.42, 0.1 greater than P greater than 0.05), or the time since clipping (r = 0.02, P greater than 0.05). There was no significant correlation between the degree of hypertension and the plasma renin activity (r = 0.42, 0.1 greater than P greater than 0.05). In rats with blood pressure drops greater than 20 mm Hg in response to 1-Sar-8-Ala-AII, the final blood pressure level was still above the normotensive range. Excision of the clipped kidney reduced blood pressure to normal or to near normal within 24 hours in all of the rats tested. It is concluded that the degree of dependence of renal hypertension on the renin-angiotensin system is directly related to the increase in circulating angiotensin itself and not to an increase in sensitivity to angiotensin. Other factors appear to be involved in renal clip hypertension in addition to circulating renin and angiotensin, especially when the measured activity of plasma renin is normal.

Topics: Angiotensin II; Animals; Blood Pressure; Dose-Response Relationship, Drug; Hypertension, Renal; Kidney; Male; Rats; Renal Artery Obstruction; Renin; Saralasin; Sodium; Stress, Physiological