Haemodynamic differences between cromakalim and pinacidil: comparison with nifedipine

Clapham, J.C.; Longman, S.D.

European Journal of Pharmacology 171(1): 109-117

1989


ISSN/ISBN: 0014-2999
PMID: 2693121
Accession: 007392725

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Abstract
The effects of cromakalim (0.015, 0.03 and 0.06 mg kg-1 p.o.), pinacidil (0.3, 0.6 and 1.2 mg kg-1 p.o.) and nifedipine (0.15, 0.3 and 0.6 mg kg-1 p.o.) were compared on mean arterial pressure (MAP), heart rate (HR), mean renal blood flow (MRBF) and plasma renin activity (PRA) in the conscious normotensive cat. All drugs elicited dose-related falls in MAP with cromakalim being about 10 times more potent than nifedipine or pinacidil, the lattter two drugs being equipotent. For similar reductions in MAP, the increases in HR and PRA produced by cromakalim were significantly smaller than those produced by either nifedipine or pinacidil. Cromakalim (0.015-0.06 mg kg-1 p.o) elicited dose-related increases in MRBF with the peak effect occurring 2-2.5 h post-dose. Thereafter, MRBF recovered toward pretreatment levels despite MAP being almost maximally reduced. Neither nifedipine nor pinacidil affected MRBF though nifedipine (0.3 mg/kg-1 p.o.) caused a significant reduction in renal vascular resistance. This study has shown that important haemodynamic differences exist between cromakalim, nifedipine and pinacidil suggesting that increased MRBF is not a general property of K+ channel activation or of Ca2+ slow channel blockade.