The vascular effects of pinacidil in trout (Oncorhynchus mykiss)

Michael P. Smith, Kenneth R. Olson

Research output: Contribution to journalArticlepeer-review

Abstract

Pinacidil (PNC) is an antihypertensive agent which exerts direct vasorelaxant effects by opening ATP-sensitive potassium channels (K+ATP) thereby hyperpolarizing vascular smooth muscle. However, K+ conductance-independent mechanisms of vasorelaxation have also been implicated. We herein present the effects of PNC in O. mykiss, to our knowledge the first investigation of K+ATP pharmacology in fish. In vitro, 10-6 to 10-4HM PNC relaxed rings of the 3rd and 4th efferent branchial and coeliaco-mesenteric arteries as well as the ventral aorta which had been precontracted with arginine vasotocin. This relaxation was variably affected by glyburide (GLY, 10-5M) but not by indomethacin or méthylène blue Interestingly, ICHvl PNC also relaxed otherwise unstimulated rings and rings precontracted with 80mM K+. In vivo, administration of 0.1 to 5 0 mg/kg i.a. PNC immediately but transiently reduced dorsal aortic pressure in conscious cannulated trout by as much as 30% ("10+2 mmHg, n=9), an effect partially inhibited by 50 mg/kg i.a. GLY. These studies demonstrate that PNC is indeed vasorelaxant in vitro and hypotensive in vim in trout However, the particular mechanisms of PNC's action require further investigation.

Original languageEnglish (US)
Pages (from-to)A341
JournalFASEB Journal
Volume10
Issue number3
StatePublished - Dec 1 1996
Externally publishedYes

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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