Chronic activation of endothelin B receptors: New model of experimental hypertension

Gregory Fink, Melissa Li, Yanny Lau, John Osborn, Stephanie Watts

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

Endothelin (ET) exerts powerful pressor actions primarily through activation of the ETA receptor subtype. The ETB receptor (ETBR) subtype, on the other hand, is generally thought to initiate physiological actions that decrease arterial pressure. Such actions include clearing ET from the bloodstream, initiating endothelium-mediated vasodilation, and facilitating renal sodium and water excretion. The effect of long-term activation of the ETBR on arterial pressure, however, never has been directly tested. In this study we evaluated cardiovascular responses to chronic (5-day) activation of ETBR in male rats using continuous intravenous infusion of the selective agonist sarafotoxin 6c. Surprisingly, we found that sarafotoxin 6c caused a sustained increase in arterial pressure that rapidly reversed on termination of infusion. The hypertension was associated with increased renal excretion of sodium and water and decreased plasma volume. Alterations in daily sodium intake did not affect the magnitude of the hypertension. Hemodynamic studies revealed a decreased cardiac output and increased total peripheral resistance during sarafotoxin 6c infusion. Infusion of sarafotoxin 6c caused a small increase in plasma ET levels. Nevertheless, the hypertension was not affected by coadministration of a selective ETA receptor antagonist (atrasentan) but was completely prevented by treatment with a combined ETA receptor and ETBR antagonist (A186280). These experiments reveal for the first time that chronic activation of ETBR in rats causes sustained hypertension.

Original languageEnglish (US)
Pages (from-to)512-518
Number of pages7
JournalHypertension
Volume50
Issue number3
DOIs
StatePublished - Sep 2007

Keywords

  • ETB receptor
  • Endothelin
  • Hemodynamics
  • Salt

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