saralasin and Hypertension--Malignant

Topics: Angiotensin II; Angiotensin Receptor Antagonists; Blood Pressure; Humans; Hypertension, Malignant; Hypertension, Renovascular; Receptors, Angiotensin; Renin; Saralasin; Teprotide

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

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

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

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

Topics: Aldosterone; Arginine Vasopressin; Blood Pressure; Cardiac Output; Heart Rate; Hemodynamics; Humans; Hypertension, Malignant; Kidney Failure, Chronic; Norepinephrine; Phentolamine; Renin; Saralasin; Stroke Volume; Vascular Resistance

We investigated the antagonistic properties of saralasin in acute and chronic angiotension II (ANG II)-dependent hypertension. Two models of experimental hypertension were studied: (a) Rats acutely infused i.v. with ANG II to raise the blood pressure (BP) by about 35 mmHg. (b) One-clip, two-kidney renal hypertensive rats. In both experimental models increasing doses of saralasin were infused i.v., and three parameters were evaluated at each dose level: (1) fall of BP, (2) plasma concentration of saralasin, and (3) plasma concentration of ANG II. It was found that saralasin led to a more pronounced fall of BP in malignant than in benign renal hypertension. To reduce BP by about 20 mmHg, saralasin plasma concentrations had to exceed those of ANG II about 2000-fold in renal hypertension and about 7-fold in rats infused with ANG II. It is concluded that saralasin antagonises ANG II more effectively in acute than in chronic hypertension.

Topics: Acute Disease; Angiotensin II; Angiotensin Receptor Antagonists; Animals; Blood Pressure; Chronic Disease; Hypertension, Malignant; Hypertension, Renovascular; Male; Rats; Rats, Inbred Strains; Receptors, Angiotensin; Saralasin

A test using saralasin, an antagonist of angiotensin II, was carried out in 9 patients with malignant or accelerated arterial hypertension, and the initial treatment was modified according to the results: if the fall in mean arterial blood pressure was greater than 10 p. cent, beta-blockers or alpha-beta blockers were prescribed alone; if not, diuretics were used concomitantly. Blood pressure response correlated with plasma renin activity and aldosterone, and the reduction in mean arterial blood pressure after 24 hours' treatment correlated with that observed with saralasin. In longer term saralasin has no predictive value with regard to the course of the hypertensive disease or the results of future treatments.

Topics: Adult; Angiotensin II; Blood Pressure; Female; Humans; Hypertension, Malignant; Male; Saralasin; Time Factors

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

The development of malignant hypertension was studied in stroke-prone spontaneously hypertensive rats (SHR) kept on 1% NaCl as drinking water. Along with salt-loading, blood pressure gradually increased and reached a severe hypertensive level (greater than 230 mmHg), which was followed by increases in urinary protein (greater than 100 (mg/250 g body wt)/day) and plasma renin concentration (PRC, from 18.9 +/- 0.1 to 51.2 +/- 19.4 (ng/ml)/h, mean +/- SD). At this stage, renal small arteries and arterioles showed severe sclerosis and fibrinoid necrosis. Stroke was observed within a week after the onset of these renal abnormalities. The dose of exogenous angiotensin II (AII) producing 30 mmHg rise in blood pressure increased with the elevation of PRC, from 22 +/- 12 to 75 +/- 36 ng/kg, which was comparable to that in rats on water. The fall of blood pressure due to an AII inhibitor, [1-sarcosine, 8-alanine]AII (10(microgram/kg)/min for 40 min) became more prominent with the increase in PRC in salt-loaded rats, but was not detected in rats on water. These findings suggest that the activation of renin-angiotensin system participates in malignant hypertension of salt-loaded stroke-prone SHR rats that show stroke signs, proteinuria, hyperreninemia, and renovascular changes.

Topics: Angiotensin II; Animals; Blood Pressure; Diet; Hypertension; Hypertension, Malignant; Kidney; Male; Rats; Renin; Saralasin; Sodium Chloride; Vascular Resistance

Topics: Adult; Catecholamines; Diazepam; Dihydralazine; Female; Furosemide; Humans; Hypertension, Malignant; Male; Metoprolol; Pheochromocytoma; Saralasin; Sympathetic Nervous System; Vanilmandelic Acid

This case report describes a patient with malignant hypertension and phaeochromocytoma in whom blockade of angiotensin II receptors by the competitive antagonist 1-sar-8-ala-angiotensin II (Saralasin) resulted in a partial correction of the elevated BP. Plasma renin activity was high and rose further during the blockade. Competitive inhibition of angiotensin II by Saralasin does not abolish the pressor effect of catecholamines. It was therefore interesting to observe that in this patient with phaeochromocytoma, independently, both alpha-adrenergic receptor blockade and angiotensin II receptor blockade were effective in lowering BP.

Topics: Adrenal Gland Neoplasms; Adrenergic alpha-Antagonists; Angiotensin II; Humans; Hypertension, Malignant; Male; Middle Aged; Pheochromocytoma; Receptors, Angiotensin; Receptors, Cell Surface; Renin; Saralasin

An understanding of the possible role of excessive angiotensin II activity in the pathogenesis of hypertension in every patient is therapeutically desirable, but it is frustrated by the lack of complete reliability of peripheral plasma measurements of renin activity. Observation of a clear-cut, supranormal decrease in blood pressure during the intravenous infusion of the angiotensin II antagonist, saralasin, has provided a far more reliable indication of the presence of an angiotensinogenic component in the hypertension. There is convincing evidence, however, that the presence of sodium-overload may prevent a decrease in blood pressure during saralasin infusion in persons known to have angiotensinogenic hypertension and that saralasin may cause a slight decrease in the blood pressure of normal subjects after natriuresis. For these reasons, it is important to study hypotensive responses to saralasin under standardized conditions after the administration of a potent diuretic and to compare the observations with those made on normal subjects under identical circumstances. This angiotensin antagonist may be used in the therapy of malignant or advanced hypertension and as an aid to therapeutic decisions in hypertensive patients who have known renal diseases, are taking oral contraceptives or have had severe trauma to the area of the kidneys. Side effects of saralasin are limited to excessive falls in blood pressure levels, mainly when vasodilators or ganglioplegic drugs are being taken at the time of the saralasin infusion, and excessive rises in blood pressure levels, especially in hypertensive subjects with "low renin" activity during high rates of saralasin infusion or after intravenous injections of large boluses. This safe and reliable drug is a valuable tool in the investigation and therapy of hypertension.

Topics: Angiotensin II; Animals; Blood Pressure; Female; Furosemide; Humans; Hypertension; Hypertension, Malignant; Rabbits; Renin; Saralasin; Sodium