AM reverses pressor response to ET-1 independently of NO in rat coronary circulation

Pietari Kinnunen, Jarkko Piuhola, Heikki Ruskoaho, István Szokodi

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Endothelin-1 (ET-1) elicits a vasoconstrictor response via ETA receptors, whereas simultaneous activation of ETB receptors triggers the release of nitric oxide (NO), which may limit the constrictor effect of ET-1. Recently, stimulation of ETs receptors has been shown to increase the secretion of adrenomedullin (AM), a newly identified vasorelaxing peptide. The present study was designed to see whether AM can oppose the vasoconstrictor response to ET-1. In the isolated perfused paced rat heart preparation, infusion of ET-1 at concentrations of 1 nmol/l for 30 min induced a significant coronary vasoconstriction, whereas it had no effect on perfusion pressure at a dose of 0.08 nmol/1. Nω-nitro-L-arginine methyl ester (L-NAME; 300 μmol/l), a potent inhibitor of NO synthase (NOS), did not change the perfusion pressure when added alone to the perfusion fluid but it unmasked the constrictor effect of ET-1 at both concentrations. In the presence of L-NAME, AM (0.03 to 1 nmol/l) markedly reversed the pressor response to ET-1 at both concentrations. Administration of AM (0.03 and 1 nmol/l) alone resulted in a dose-dependent decrease in perfusion pressure, which was not modified in the presence of L-NAME. In conclusion, the coronary vasoconstrictor response to ET-1 is markedly augmented in the presence of a NOS inhibitor. This constrictor response is substantially reversed by AM. Our results indicate that AM may serve as a paracrine modulator of ET-1-induced vasoconstriction independently of the NO pathway.

Original languageEnglish
Pages (from-to)H1178-H1183
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume281
Issue number3 50-3
DOIs
Publication statusPublished - 2001

Keywords

  • Coronary vasoconstriction
  • N-nitro-L-arginine methyl ester
  • Perfused rat heart

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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