Accentuated vascular and endocrine response to SQ 20881 in hypertension.
We assessed vascular and hormonal responses to inhibition of peptidyldipeptide hydrolase, which converts angiotensin I to angiotensin II (converting enzyme) and degrades bradykinin (kininase II), in subjects given 10 meq of sodium to activate both systems. In nine normal subjects a threshold dose of 30 MICROgram per kilogram of the inhibitor, SQ 20881, modestly influenced mean blood pressure (-5 +/- 1 mm Hg, P less than 0.05), and renal blood flow (+50+/-8 ml per 100 g per minute), plasma renin activity (+ 2.3 +/- 0.6 ng per milliliter per hour), and angiotensin II (-11 +/- 3 pg per milliliter) more strikingly (P less than 0.01). In six patients with essential hypertension the threshold inhibitor dose was reduced to 10 microgram per kilogram; 30 kilogram per kilogram had an enhanced (P less than 0.01) effect on mean blood pressure (-11 +/- 2 mm Hg), renal blood flow (137 +/- 20 ml per 100 g per minute), and angiotensin II concentration (-29 +/- 12 pg per milliliter). SQ 20881 elevated plasma bradykinin concentration (7.4 +/- 2.6 ng per milliliter, P less than 0.02) only in the hypertensive patients. Because both renin-angiotensin and kallikrein-bradykinin systems are influenced, vascular responses to SQ 20881 must be interpreted cautiously, but this agent has excellent antihypertensive characteristics.
D000804:Angiotensin II / Q000097:blood*; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D001794:Blood Pressure / Q000187:drug effects*; D001920:Bradykinin / Q000097:blood; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology; D007668:Kidney / Q000098:blood supply*; D009842:Oligopeptides / Q000494:pharmacology*; D012039:Regional Blood Flow / Q000187:drug effects; D012083:Renin / Q000097:blood*; D013722:Teprotide / Q000008:administration & dosage / Q000494:pharmacology*
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D009842:Oligopeptides; D000804:Angiotensin II; D013722:Teprotide; D012083:Renin; D001920:Bradykinin