Positive inotropic effects of calcium channel antagonists are not necessarily caused by partial calcium channel agonism.
Recently it has been reported that some dihydropyridine calcium channel antagonists (nifedipine, nimodipine, nitrendipine) are able to produce positive inotropic effects in isolated perfused guinea pig hearts. We studied the effects of nifedipine in isolated perfused paced rat hearts under constant pressure and constant flow perfusion conditions. We found that nifedipine is able to produce a positive inotropic effect under constant pressure conditions but not under constant flow conditions. We conclude that nifedipine does not have partial calcium channel agonistic properties and that the positive inotropic effect seen under constant pressure conditions is a result of the vasodilating properties of the drug. Positive inotropic effects caused by vasodilatation can be explained by the "garden-hose-effect".
Punt
N C
NC
Department of Pharmacology and Therapeutics, University of Groningen, The Netherlands.
van Amsterdam
F T
FT
Goddijn
M M
MM
Haas
M
M
Zaagsma
J
J
D000818:Animals; D001783:Blood Flow Velocity; D002120:Calcium Channel Agonists; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003326:Coronary Circulation; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009543:Nifedipine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D002120:Calcium Channel Agonists; D002121:Calcium Channel Blockers; D009543:Nifedipine