[Cardiovascular effects of peptide inhibitors of the renin-substrate reaction in rats with renovascular hypertension. Goldblatt: 2 kidneys--1 clip]

Arch Mal Coeur Vaiss. 1988 Jun:81 Spec No:183-7.
[Article in French]

Abstract

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.

Publication types

  • English Abstract

MeSH terms

  • Animals
  • Blood Pressure / drug effects
  • Cardiac Output / drug effects
  • Heart Rate / drug effects
  • Hemodynamics / drug effects*
  • Hypertension, Renovascular / drug therapy*
  • Male
  • Oligopeptides / pharmacology
  • Oligopeptides / therapeutic use*
  • Rats
  • Rats, Inbred Strains
  • Vascular Resistance / drug effects

Substances

  • Oligopeptides
  • AG 84-10
  • AG 85-12