Effects of the angiotensin II antagonist 1-sar-8-ala-angiotensin II in hypertension in man.
The angiotensin II antagonist 1-sar-8-ala-angiotensin II (saralasin) was infused in forty-six patients with hypertension of various aetiology (essential, renal arterial or parenchymal disease, primary hyperaldosteronism), before and/or during sodium volume depletion obtained by chlorthalidone and low sodium diet. When saralasin was infused in twenty-five patients ingesting 130 mmol of sodium per day, including patients with proven renovascular hypertension, the changes in mean arterial pressure and ranged from +10 to -7 mmHg (mean: +0.20 mmHg) and were not related to the plasma renin concentration (PRC) (r = -0.11). During sodium volume depletion, saralasin induced changes in mean arterial pressure, ranging from +21 to -76 mmHg, which were closely related to log PRC (n = 32; r = -0.87). Combined sodium depletion and antagonism of angiotensin II 'normalized' mean arterial pressure (less than or equal to 100 mmHg) in twenty-one of the thirty-two patients, while pressure remained between 106 and 147 mmHg in eleven 'poor' responders, so that pressor mechanisms other than sodium volume and angiotensin must be responsible for the remaining elevation of pressure in these patients. The study indicates that arterial pressure is not dependent on the immediate pressor effects of angiotensin II in sodium replete patients, and in sodium deplete subjects whose PRC remains low, while it is at least partly angiotensin II dependent during sodium volume depletion in the others. The results cast doubts on the clinical usefulness of saralasin in the investigation of patients with hypertension, when studied in the conditions of the present study.
D000328:Adult; D000804:Angiotensin II / Q000031:analogs & derivatives*; D001794:Blood Pressure / Q000187:drug effects; D005260:Female; D006801:Humans; D006973:Hypertension / Q000201:enzymology / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D012083:Renin / Q000097:blood; D012504:Saralasin / Q000494:pharmacology*; D012964:Sodium / Q000502:physiology
D000804:Angiotensin II; D012964:Sodium; D012083:Renin; D012504:Saralasin