Intracerebroventricularly applied peptidase inhibitors increase endogenous angiotensin levels

Brain Res. 1990 Oct 8;529(1-2):126-30. doi: 10.1016/0006-8993(90)90819-w.

Abstract

Rats received the aminopeptidase inhibitors amastatin (AM) and bestatin (BE), and carboxypeptidase inhibitor Plummer's (PL) via intracerebroventricular infusion in various combinations, i.e. PL alone, AM + BE, and a cocktail consisting of AM + BE + PL. Blood pressure responses were recorded and a postinfusion sample of cerebrospinal fluid (CSF) was radioimmunoassayed for endogenous angiotensin levels. Results indicate that CSF angiotensin was increased approximately 1.5x over control levels when PL was infused; a 2.5x increase accompanied AM + BE administration; and a 10.3x elevation was measured when all 3 inhibitors were infused as a cocktail. Concomitant elevations in blood pressure accompanied increased concentrations of angiotensin. We conclude that endogenous levels of angiotensin can be significantly increased in the ventricular space when a combination of these inhibitors is utilized to protect both the amino and carboxyl terminals of the angiotensin molecule from enzymatic degradation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 3-Mercaptopropionic Acid / analogs & derivatives*
  • 3-Mercaptopropionic Acid / pharmacology
  • Angiotensin II / cerebrospinal fluid*
  • Angiotensin III / cerebrospinal fluid*
  • Animals
  • Anti-Bacterial Agents*
  • Blood Pressure / drug effects
  • Carboxypeptidases / antagonists & inhibitors
  • Cerebral Ventricles / drug effects
  • Cerebral Ventricles / physiology*
  • Injections, Intraventricular
  • Leucine / administration & dosage
  • Leucine / analogs & derivatives*
  • Leucine / pharmacology
  • Male
  • Oligopeptides / administration & dosage
  • Oligopeptides / pharmacology
  • Peptides*
  • Protease Inhibitors / pharmacology*
  • Radioimmunoassay
  • Rats
  • Rats, Inbred Strains

Substances

  • Anti-Bacterial Agents
  • Oligopeptides
  • Peptides
  • Protease Inhibitors
  • Angiotensin II
  • Angiotensin III
  • amastatin
  • 2-mercaptomethyl-3-guanidinoethylthiopropionic acid
  • 3-Mercaptopropionic Acid
  • Carboxypeptidases
  • Leucine
  • ubenimex