[Cardiovascular effects of peptide inhibitors of the renin-substrate reaction in rats with renovascular hypertension. Goldblatt: 2 kidneys--1 clip].
The antihypertensive effects of 2 different peptidic substrate analogs: AG 84-10 AG 85-12 were investigated in renovascular hypertensive (Goldblatt, 2 kidneys--1 clip) Sprague-Dawley male rats. AG 84-10 (Ac-Pro-Phe-His-Leu-Val-Tyr) is similar to Angiotensinogen 6-13 and AG 85-12 (Ac-Ile-His-Pro-Phe-His-Leu) mimics the C-terminal portion of Angiotensin I. 6 weeks after clipping, hemodynamic profiles of these molecules [Heart rate (HR), mean arterial pressure (MAP), filling parameters, peripheral vascular resistances (PR) and cardiac output (CO)] during 90 minutes, were determined in the anesthetized animals. CO was measured using a thermodilution technique. Parallel radio-immunologic dosages of plasma renin activity were performed. Measurements and calculation of previously defined hemodynamic variables, every 10 minutes, demonstrated that: AG 84-10 exerted an early but transient decrease of MAP and PR, an increase of CO without modification of other hemodynamic parameters. AG 85-12 induced a late and durable decrease of MAP and PR with a significant decrease of heart rate, but without modification of CO and other hemodynamic variables. Example: PR mmHg/ml/mn/kg (mean +/- SD): *p less than 0.05 ** p less than 0.01. (Table: see text). The different levels of plasma renin activity were in accordance with hemodynamic data. So, the 2 peptidic substrate analogs elicited antihypertensive effects with a more efficient action of AG 85-12.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006978:Hypertension, Renovascular / Q000188:drug therapy*; D008297:Male; D009842:Oligopeptides / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D011919:Rats, Inbred Strains; D014655:Vascular Resistance / Q000187:drug effects
D009842:Oligopeptides; C057511:AG 84-10; C057512:AG 85-12
Effets cardio-vasculaires d'inhibiteurs peptidiques de la réaction rénine-substrat chez le rat atteint d'hypertension réno-vasculaire. Goldblatt: 2 reins--1 clip.