Effects of central endothelin-1 in normotensive and spontaneously hypertensive rats

Bull Exp Biol Med. 2003 Mar;135(3):237-40. doi: 10.1023/a:1024172611834.

Abstract

Changes in blood pressure and sympathetic nerve activity induced by local injection of endothelin-1 into the rostroventrolateral medulla were studied in narcotized stroke-prone spontaneously hypertensive rats (SHRSP) and normotensive WKY rats. Endothelin-1 produced similar biphasic response in both rat strains: a transient increase in blood pressure and sympathetic nerve activity followed by progressive hypotension and bradycardia. Pretreatment with ETB-receptor antagonist BQ788 inhibited sympathetic activation induced by endothelin-1, while pretreatment with the ETA-receptor antagonist N-acetyl-[D-Trp16]-endothelin-1 abolished the subsequent hypotension. The antihypotensive effect of ETA-receptor blockade was most effective in normotensive rats. Our findings suggest that cardiovascular disorders in SHRSP rats can be related to peculiarities in the rostroventrolateral medullar endothelin system.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antihypertensive Agents / metabolism
  • Blood Pressure / drug effects*
  • Endothelin-1 / administration & dosage
  • Endothelin-1 / metabolism
  • Endothelin-1 / pharmacology*
  • Heart Rate / drug effects*
  • Male
  • Medulla Oblongata / drug effects
  • Oligopeptides / metabolism
  • Piperidines / metabolism
  • Rats
  • Rats, Inbred SHR
  • Rats, Inbred WKY
  • Receptors, Endothelin / metabolism
  • Sympathetic Nervous System / drug effects*
  • Sympathetic Nervous System / metabolism

Substances

  • Antihypertensive Agents
  • Endothelin-1
  • Oligopeptides
  • Piperidines
  • Receptors, Endothelin
  • BQ 788