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 language||English (US)|
|State||Published - Dec 1 1996|
ASJC Scopus subject areas
- Molecular Biology