Cardiovascular effects of a renin inhibitor in relation to posture in nonhuman primates

Clin Exp Hypertens A. 1985;7(1):105-21. doi: 10.3109/10641968509074757.

Abstract

Orthostatic cardiovascular reflexes were evaluated in conscious cynomolgus monkeys during interruption of the renin-angiotensin system with the renin inhibitor: RIP (Pro-His-Pro-Phe-His-Phe-Phe-Val-Tyr-Lys-OH). RIP was synthesized via solid phase techniques and purified to homogeneity. In vitro studies indicated that it exhibited classical competitive inhibition of renin with a KI of 2.3 microM. In vivo, RIP at 2 mg/kg per min inhibited renin and angiotensin I pressor responses indicating that it was not a specific renin inhibitor at this dose. However, in spite of the nonspecificity, RIP did not affect the supine blood pressure of sodium-replete monkeys, but did evoke hypotension in supine sodium depleted monkeys. RIP did not elicit significant orthostatic hypotension in either sodium-replete or sodium depleted monkeys. The cardiovascular effects of RIP described in this study appear to be due to inhibition of the renin-angiotensin system.

MeSH terms

  • Angiotensin I / metabolism
  • Angiotensin II / administration & dosage
  • Angiotensin II / antagonists & inhibitors
  • Angiotensin-Converting Enzyme Inhibitors
  • Animals
  • Binding, Competitive
  • Blood Pressure / drug effects
  • Humans
  • Hypotension, Orthostatic / chemically induced
  • Macaca fascicularis
  • Male
  • Oligopeptides / pharmacology*
  • Oligopeptides / toxicity
  • Posture
  • Reflex / drug effects
  • Renin / antagonists & inhibitors
  • Renin-Angiotensin System / drug effects*
  • Saralasin / pharmacology
  • Sodium / administration & dosage
  • Sodium / deficiency

Substances

  • Angiotensin-Converting Enzyme Inhibitors
  • Oligopeptides
  • Angiotensin II
  • renin inhibitory peptide
  • Angiotensin I
  • Sodium
  • Renin
  • Saralasin