These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Cardiovascular and renal actions of the endothelin(B) receptor in pigs.
    Author: Cirino M, Martin E, Yano M, Rodger IW.
    Journal: J Cardiovasc Pharmacol; 1997 Jun; 29(6):704-12. PubMed ID: 9234650.
    Abstract:
    Previously we showed that blocking the endothelin (ET)A receptor subtype with BQ-153 inhibited the vasoconstrictor effects of intravenously administered ET-1. In the presence of the ET(A) antagonist, ET-1 produced marked reductions in myocardial contractility and renal blood flow. We postulated that either the ET(B) receptor, or some other, as yet unidentified, ET-receptor subtype mediated the observed hemodynamic changes. In anesthetized pigs, this hypothesis was tested by using a recently developed selective, high-affinity antagonist to the ET(B) receptor, BQ-788, and sarafotoxin S6c, a selective ET(B) agonist, to determine the contribution of this receptor subtype to cardiovascular function. Endothelin-1 (0.4 nmol/kg, i.v.) produced the characteristic biphasic hemodynamic responses, consisting of an initial transient reduction in mean arterial pressure (MAP; 83 +/- 3 to 72 +/- 4 mm Hg; n = 9) followed by a prolonged increase (112 +/- 4 mm Hg; p < 0.01). As well, cardiac output (-58%; p < 0.05), myocardial contractility (-19%; p < 0.01), and renal blood flow (63%; p < 0.05) decreased. Sarafotoxin S6c produced marked but transient reductions in MAP (p < 0.001), cardiac output (p < 0.01), myocardial contractility (p < 0.001), and renal blood flow (p < 0.05). BQ-788 (1.0 mg/kg, i.v.), administered 3 min before sarafotoxin S6c, inhibited its effects. BQ-788 also inhibited the initial transient reduction in MAP seen after the injection of ET-1, but the subsequent sustained pressor responses were enhanced as reflected in the greater increases in left ventricular pressure (p < 0.02), myocardial contractility (p < 0.05), MAP (p < 0.01), and a larger reduction in cardiac output (p < 0.05). The heart rate was not changed after the initial ET injection, but it increased 54% when the peptide was administered in the presence of BQ-788. The reduction in renal blood flow was still evident, and its magnitude (64%) remained the same (p < 0.01) after treatment with BQ-788. Only the combined administration of both the ET(A) (BQ-123) and ET(B) (BQ-788) receptor antagonists blocked the effects of ET-1 on renal blood flow (p < 0.05). These data confirm that BQ-788 is a selective and effective antagonist of the ET(B) receptor and show that activation of this receptor subtype is involved in the transient vasodilation provoked by ET-1. Additionally, the ET(B) receptor appears to oppose the vasoconstrictor effects of the ET(A) receptor, which clearly mediates vasoconstriction. Combined treatment with BQ-123 and BQ-788 attenuated the reductions in renal blood flow produced by ET-1. Furthermore, some actions of ET-1 were not blocked by these antagonists and cannot be attributed to either the ET(A) or ET(B) receptors. We hypothesize the existence of an additional ET receptor or a subtype of the ET(B) receptor that is insensitive to BQ-788.
    [Abstract] [Full Text] [Related] [New Search]