saralasin and Renal-Artery-Obstruction

Topics: Adult; Antihypertensive Agents; Child; Costs and Cost Analysis; Female; Humans; Hypertension, Renovascular; Male; Middle Aged; Radiography; Renal Artery; Renal Artery Obstruction; Renal Veins; Renin; Saralasin

Although clinical reports have suggested that antihypertensive therapy can control blood pressure in patients with renovascular hypertension, adequate randomized studies comparing medical versus surgical management are lacking. It is well recognized that progressive deterioration in renal function can occur despite good blood pressure control. Recent experience suggests that higher-risk patients with atherosclerotic renovascular hypertension can benefit from an aggressive surgical approach, whereas newer medical therapies capable of specific inhibition of the renin-angiotensin system suggest greater potential benefits to other patients. Properly performed randomized trials comparing medical versus surgical therapy of renovascular hypertension are needed.

Topics: Adult; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Arteriosclerosis; Atenolol; Captopril; Dipeptides; Enalapril; Female; Humans; Hypertension, Renovascular; Male; Metoprolol; Middle Aged; Nadolol; Pindolol; Propanolamines; Propranolol; Renal Artery Obstruction; Renin-Angiotensin System; Saralasin; Timolol

The renal arteriogram alone, useful as an anatomic guide for the surgeon or radiologist, is inadequate to predict potential blood pressure reversal by correction of the obstructing lesion. A patient must be identified as having functionally significant renal arterial disease before intervention can be recommended. The authors discuss uncovering functionally significant renal artery stenosis, the pathophysiology of experimental Goldblatt hypertension, and criteria to identify renovascular hypertension, including peripheral plasma renin activity and differential renal-vein renin determinations.

Topics: Adult; Age Factors; Angiotensin II; Blood Pressure; Captopril; Female; Humans; Hypertension, Renovascular; Kidney Function Tests; Male; Middle Aged; Models, Biological; Renal Artery Obstruction; Renal Circulation; Renal Veins; Renin; Saralasin; Smoking; Teprotide

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

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

Angiotensin antagonists have become useful tools in studying pharmacologic and pathophysiologic roles of the renin-angiotensin axis. Several of these uses are described herein. Their value as t-ols in the diagnosis of renal artery stenosis is yet to be determined.

Topics: Aldosterone; Angiotensin II; Blood Pressure; Humans; Hypertension; Kidney; Kinetics; Propranolol; Renal Artery Obstruction; Renal Veins; Renin; Saralasin; Vasodilator Agents; Water-Electrolyte Balance

Hypertension was produced in cynomolgus monkeys by reducing blood flow to the left kidney by 60% via renal artery stenosis (2-kidney, 1-clip). Significant increases in mean arterial blood pressure (MABP) were observed within two to three weeks. Maximum increase (from 95 +/- 6 mmHg to 130 +/- 7 mmHg) occurred at about four to six weeks following renal artery stenosis and was sustained for more than 24 weeks. Plasma renin activity (PRA) was elevated concomitantly with the increase in MABP. PRA was raised to 42 +/- 3 ng angiotensin I/ml/hr six weeks after renal artery stenosis from a control PRA of 3 +/- 0.7 ng angiotensin I/ml/hr. At six months post renal artery stenosis, PRA was 33.4 +/- 4.2 ng angiotensin I/ml/hr. The angiotensin II (AII) receptor antagonist saralasin, the angiotensin I converting enzyme inhibitor captopril, and the renin inhibitor CGP 38,560 produced sustained reductions in MABP. The antihypertensive response to the renin inhibitor CGP 38,560 was associated with a reduction in PRA of greater than 99%, and a greater than 90% reduction in immunoreactive AII. These studies demonstrate that high-renin hypertension can be induced in the cynomolgus monkey. This pathological model provides a useful method for investigating the antihypertensive effects of agents which antagonize the renin-angiotensin system in a nonhuman primate.

Topics: Angiotensin II; Animals; Blood Pressure; Captopril; Disease Models, Animal; Hypertension, Renovascular; Macaca fascicularis; Male; Oligopeptides; Renal Artery Obstruction; Renin; Saralasin

Topics: Adult; Aged; Angiography, Digital Subtraction; Humans; Hypertension, Renovascular; Middle Aged; Radioisotope Renography; Renal Artery Obstruction; Renin; Saralasin; Urography

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

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

Eighty-six hypertensive patients with arteriographic evidence of renal artery stenosis presented between 1968 and 1979. Thirty-nine subsequently underwent surgery and were followed thereafter for at least one year. In 54 per cent blood pressure was reduced to within one standard deviation of the mean for a normal individual of the same sex and age. A further thirty-one per cent of patients were 'improved', but needed hypotensive drugs to maintain blood pressure within this range. In the remaining 15 per cent of patients the operation did not reduce blood pressure. The purpose of the study was to assess our ability to predict this varies surgical outcome using clinical observations and special tests. The latter included measurement of plasma renin concentration in both peripheral vein and renal vein plasma, catheterization of both ureters and studies of the response of blood pressure to brief infusion of saralasin. No single observation or test, no combination of observations or tests and no discriminant function clearly separated patients in whom surgery would succeed from those in whom it would fail. Renal vein renin ratio was the best test; all patients with a ratio greater than 2.0 underwent successful surgery, but so too did some patients with a lower ratio. We also analysed the factors which had influenced our decision to undertake special investigations in 65 of the 86 patients and, having done these investigations, to recommend surgery in 39. No single factor seemed to have had overriding importance in making these decisions.

Topics: Adolescent; Adult; Aged; Child; Female; Humans; Hypertension, Renovascular; Male; Middle Aged; Prognosis; Renal Artery Obstruction; Renal Veins; Renin; 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

One-kidney rabbits were subjected to renal artery stenosis, and acute experiments were performed 3 days later on conscious animals; one-kidney rabbits without renal artery stenosis served as controls. Rabbits with 3-day renal artery stenosis were normotensive and had normal values for plasma renin activity. Intravenous infusion of arginine vasopressin at 5 mU.min-1.kg body wt-1 for 5 min resulted in a significantly (P less than 0.01) greater increase in mean arterial pressure and total peripheral resistance (TPR) in the renal artery stenosis rabbits than in the controls. Infusion of the angiotensin II (AII) competitive antagonist, [Sar1, Ile8]AII, before the vasopressin infusion abolished the hyperresponsiveness to vasopressin in the renal artery stenosis rabbits and resulted in changes in mean arterial pressure and TPR that were approximately of the same magnitude as the controls. Infusion of [SAr1, Ile8]AII before vasopressin infusion in control rabbits did not alter the cardiovascular responses to vasopressin. Because previous studies have shown that 3-day renal artery stenosis rabbits have exaggerated pressor responses to norepinephrine and that this hyperresponsiveness to norepinephrine is blocked by [Sar1, Ile8]-AII, the present study with vasopressin provided evidence that the increased responsiveness in this model is not specific for a single pressor agent. These studies also demonstrated that AII plays an important role in mediating the exaggerated pressor responses to vasopressin in this prehypertensive model.

Topics: Animals; Blood Pressure; Cardiac Output; Cold Temperature; Denervation; Forelimb; Heart; Heart Rate; Male; Perfusion; Rabbits; Renal Artery Obstruction; Renin; Saralasin; Skin; Vascular Resistance

Infusion of thrombin and the fibrinolysis inhibitor tranexamic acid during ether anaesthesia in the rat gives rise to fibrin deposition in the renal glomeruli. This resulted in renal insufficiency as indicated by an increase in the serum urea nitrogen, reduction in the renal blood flow and patchy cortical necrosis in the kidneys. The plasma renin activity was elevated initially probably due to the ether anaesthesia. Infusion of the angiotensin II antagonist saralasin prevented the renal insufficiency if it was given during the thrombin infusion but not if it was given afterwards. The deposition of fibrin in the kidneys was also reduced. The results indicate that angiotensin II is involved in the pathogenesis of the renal injury.

Topics: Acute Kidney Injury; Angiotensin II; Animals; Female; Fibrin; Rats; Rats, Inbred Strains; Renal Artery Obstruction; Renal Circulation; Renin; Renin-Angiotensin System; Saralasin; Thrombin

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

Determinants of glomerular ultrafiltration were studied by micropuncture in clamped (n = 11) and unclamped (n = 7) kidneys of two-kidney hypertensive rats and compared to 15 controls. Infusion of the angiotensin II antagonist and saralasin lowered the blood pressure significantly. Glomerular capillary pressure (PGC) in clamped kidneys was decreased to 56 +/- (SD) 3 vs. 61 +/- 3 mm Hg in controls. Early proximal flow rate (EPFR) was decreased to 20 +/- 1 vs. 26 +/- 2 nl/min in controls, at an unchanged single nephron filtration fraction (SNFF), indicating a reduced glomerular plasma flow (SNGPF). Preglomerular resistance (RA) was increased by 21%. In unclamped kidneys PGC was increased to 65 +/- 2 mm Hg. EPFR was increased to 32 +/- 2 nl/min, indicating, at an unchanged SNFF, an increased SNGPF. RA increased by 51%, whereas postglomerular resistance declined by 25%. The ultrafiltration coefficient was reduced by 24% in unclamped kidneys. Our results indicate that in clamped kidneys an increase of RA causes a reduction of PGC and hence a reduction of pressure at the baroreceptor site which may act as a trigger mechanism for renin release.

Topics: Animals; Disease Models, Animal; Glomerular Filtration Rate; Hypertension; Kidney; Kidney Tubules, Proximal; Rats; Renal Artery Obstruction; Saralasin

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: Angiotensin II; Diastole; Furosemide; Humans; Hypertension; Hypertension, Renovascular; Infusions, Parenteral; Pressoreceptors; Renal Artery Obstruction; Renin; Saralasin; Sodium; Time Factors

Topics: Adult; Angiotensin II; Blood Pressure; Cardiac Volume; Heart Rate; Hemodynamics; Humans; Hypertension; Middle Aged; Plasma Volume; Pressoreceptors; Renal Artery Obstruction; Renin; Saralasin; Vascular Resistance

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

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

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

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

Plasma renin activity (PRA) and concentration, measured after acid treatment of the plasma (PRC3.3), were determined on the same plasma samples in different conditions. Log PRA and log PRC3.3 were significantly (P less than 0.001) and similarly related to sodium intake, age, and plasma aldosterone concentration in normal subjects. The correlation coefficient between log PRA and log PRC3.3 was 0.49 in 80 sodium-replete and sodium-deplete normal subjects, and it was 0.84 in 84 hypertensive patients untreated or under treatment with thiazides. On the contrary, during beta adrenergic blockade, PRA decreased significantly (P less than 0.001) by 62% while the changes in PRC3.3 were not significant. At maximal exercise, PRA increased significantly by 168% while the PRC3.3 increase of 24% was not significant. In hypertensive patients with unilateral renal artery stenosis the ipsilateral renal vein/artery ratio was higher for PRA (2.46) than for PRC3.3 (1.56), whereas both ratios on the controlateral side were similar and close to one (1.14 and 1.06). The conditions in which PRA and PRC3.3 determinations are concordant or discordant are discussed.

Topics: Adult; Age Factors; Aged; Aldosterone; Angiotensin II; Diet; Diet, Sodium-Restricted; Female; Humans; Hypertension; Male; Metoprolol; Middle Aged; Physical Exertion; Renal Artery Obstruction; Renal Veins; 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 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

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

Acute renal artery stenosis in hydropenic dogs caused a contralateral increase in urine volume and free water clearance without change in glomerular filtration, renal blood flow, or osmolar clearance. The increase in urine volume was not dependent on the development of hypertension since it occurred in animals pretreated with trimethaphan but was dependent upon angiotensin since it was presented with angiotensin blockade with Saralasin. The effect was not caused by angiotensin inhibiting antidiuretic hormone release since the polyuria occurred in hypophysectomized animals receiving a constant infusion of 10 muU/kg per min of aqueous Pitressin. Since the rise in urine volume was associated with an increase in renal vein prostaglandin E concentration and was prevented by pretreatment with indomethacin (5 mg/kg) the results suggest that the rise in plasma angiotensin after renal artery stenosis causes an increase in contralateral prostaglandin E synthesis with resultant antagonism to antidiuretic hormone at the collecting tubule.

Topics: Animals; Blood Pressure; Dogs; Glomerular Filtration Rate; Indomethacin; Polyuria; Prostaglandins E; Renal Artery Obstruction; Renin; Saralasin; Sodium; Trimethaphan; Vasopressins

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

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; Animals; Blood Pressure; Disease Models, Animal; Dogs; Enzyme Inhibitors; Humans; Hypertension; Pindolol; Propranolol; Rats; Renal Artery Obstruction; Renin; Saralasin

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

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

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 angiotensin II (AII) such as saralasin might theoretically be of great value in the recognition of angiotensinogenic hypertension. Evidence is presented to show the importance of overcoming any existing sodium overload and of administering saralasin first in small and then in larger amounts by infusion (or injection). When this was done in 600 hypertensive patients, 62 showed a fall in blood pressure of more than 10/8 mm Hg. Further tests in 50 of these subjects indicated that the fall in blood pressure was associated with high peripheral levels of plasma renin activity (PRA) and/or abnormal renal vein PRA ratios in 94%. The procedure rarely failed to detect even mild forms of angiotensinogenic hypertension. In 62 patients found to have angiotensinogenic hypertension, the responsible lesions included unilateral renal arterial stenosis with good contralateral renal function (29%), bilateral renal disease (21%), Cushing's syndrome (6%), small vessel disease or specific excess of renin production - without other detectable renal disease - (31%) and incompletely evaluated disorders (13%). Saralasin has been of great value in simply and reliably demonstrating the presence or absence of an angiotensinogenic component in a large group of hypertensive patients.

Topics: Adult; Angiotensin II; Animals; Blood Pressure; Cushing Syndrome; Drug Administration Schedule; Humans; Hypertension; Kidney; Male; Rats; Renal Artery Obstruction; Renal Veins; Renin; Saralasin; Sodium

The effect of saralasin in lowering blood pressure and plasma aldosterone concentration in normal subjects, both sodium-replete and sodium-deplete, and in patients with various forms of hypertension, is closely related to the basal plasma angiotensin II concentration. These findings confirm and extend earlier studies of angiotensin II/arterial pressure and angiotensin II/aldosterone dose-response curves. They also emphasize the importance of the renin-angiotensin system in the control of aldosterone in sodium depletion and in renal hypertension.

Topics: Aldosterone; Angiotensin II; Blood Pressure; Diet; Humans; Hyperaldosteronism; Hypertension; Kidney Failure, Chronic; Male; Renal Artery Obstruction; Renin; Saralasin; Sodium; Time Factors

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

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

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

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

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

Partial occlusion of the renal artery (RAO) was induced in dogs anesthetized with pentobarbital or morphine chloralose-urethan. The effect of [Sar1, Ala8]angiotensin II (P-113) was compared before and during RAO on blood flow and vascular resistance of the contralateral kidney. An increase in renin secretion rate was obtained in the ischemic kidney, which was accompanied by an increase in renal vascular resistance (RVR) in the contralateral kidney and a rise in systemic blood pressure. P-113 given intra-arterially to the contralateral kidney consistently increased renal blood flow and decreased RVR during RAO, but did not alter RVR significantly before RAO. The elevation in renin secretion rate decreased between 30 and 122 min after the initiation of RAO in the pentobarbital-anesthetized dogs but not in the chloralose-urethan-anesthetized dogs. These experiments indicate that during RAO release of renin causes, through formation of angiotensin, an increase in RVR in the contralateral kidney and intra-arterial administration of P-113 restores the vascular resistance to a near-normal level.

Topics: Anesthetics; Angiotensin II; Animals; Blood Pressure; Chloralose; Dogs; Female; Kidney; Male; Phenobarbital; Regional Blood Flow; Renal Artery Obstruction; Renin; Saralasin; Vascular Resistance