Summary
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-hoseeffect”.
This is a preview of subscription content, log in via an institution to check access.
References
Abel RM, Reis RL (1970) Effects of coronary blood flow and perfusion pressure on left ventricular contractility in dogs. Circ Res 27:961–971
Amsterdam FThM van, Zaagsma J (1988) Stereoisomers of calcium antagonists discriminate between coronary vascular and myocardial sites. Naunyn-Schmiedeberg's Arch Pharmacol 337:213–219
Amsterdam FThM van, Haas M, Zaagsma J (1987) Dynamic and kinetic differences of the vascular and myocardial effects of calcium antagonists in the rat heart. J Cardiovasc Pharmacol 9:570–577
Arnold G, Kosche F, Miessner E, Neitzert A, Lochner W (1968) The importance of the perfusion pressure in the coronary arteries for the contractility and the oxygen consumption of the heart. Pflügers Arch 299:339–356
Bechem M, Schramm M (1987) Calcium-agonists. J Moll Cell Cardiol 19:63–75
Boyd RA, Giacomini JC, Wong FM, Nelson WL, Giacomini KM (1987) Comparison of binding affinities and negative inotropic potencies of the 1,4-dihydropyridine calcium channel blockers in rabbit myocardium. J Pharmacol Exp Ther 243:118–125
Drake-Holland AJ, Pugh S, Noble MIM, Mills C (1987) Problem of measuring the positive inotropic property of a vasodilating drug: an illustration using felodipine. Cardiovasc Res 21: 631–636
Döring HJ, Dehnert H (1985) Das isolierte perfundierte Herz nach Langendorff. Biomesstechnik-Verlag March GmbH, pp 102
Finet M, Godfraind T, Khoury G (1985) The positive inotropic action of the nifedipine analogue, Bay K 8644, in guinea-pig and rat isolated cardiac preparations. Br J Pharmacol 86: 27–32
Gregg DE (1963) Effect of coronary perfusion pressure or coronary flow on oxygen usage of the myocardium. Circ Res 13:497–500
Hess P, Lansman JB, Tsien RW (1984) Different modes of Ca channel gating behaviour favoured by dihydropyridine Ca agonists and antagonists. Nature 311:538–544
Himori N, Ono H, Taira N (1976) Simultaneous assessment of effects of coronary vasodilators on the coronary blood flow and myocardial contractility using the blood perfused canine papillary muscle. Jpn J Pharmacol 26:427–435
Ishii K, Taira N, Yanagisawa T (1985) Differential antagonism by Bay K 8644, a dihydropyridine calcium agonist, of the negative inotropic effects of nifedipine, verapamil, diltiazem and manganese ions in canine ventricular muscle. Br J Pharmacol 84:577–584
Ljung B, Kjellstedt A, Orebäck B (1987) Vascular versus myocardial selectivity of calcium antagonists studied by concentration-time-effect relations. J Cardiovase Pharmacol 10:S34-S39
Miller WP, Shimamoto N, Nellis SH, Liedtke AJ (1987) Coronary hyperperfusion and myocardial metabolism in isolated and intact hearts. Am J Physiol 253:1271–1278
Opie LH (1965) Coronary flow rate and perfusion pressure as determinants of mechanical function and oxidative metabolism of isolated perfused rat heart. J Physiol 180:529–541
Pettersson K, Noble MIM, Björkman JA, Hynd J, Drake-Holland AJ (1987) The positive inotropic effect of felodipine in isovolumically beating dog heart. J Cardiovasc Pharmacol 10:S112-S118
Schwartz A, Grupp IL, Grupp G, Williams JS, Vaghy PL (1984) Effects of dihydropyridine calcium channel modulators in the heart: Pharmacological and radioligand binding correlations. Biochem Biophys Res Commun 125:387–394
Strauer BE (1974) Inotropic effects of nifedipine: A new coronary dilating agent. Int J Clin Pharmacol 9:101–107
Thomas G, Groß R, Schramm M (1984) Calcium channel modulation: Ability to inhibit or promote calcium influx resides in the same dihydropyridine molecule. J Cardiovasc Pharmacol 6:1170–1176
Author information
Authors and Affiliations
Additional information
Send offprint requests to N. C. Punt at the above address
Rights and permissions
About this article
Cite this article
Punt, N.C., van Amsterdam, F.T.M., Goddijn, M.M. et al. Positive inotropic effects of calcium channel antagonists are not necessarily caused by partial calcium channel agonism. Naunyn-Schmiedeberg's Arch Pharmacol 338, 211–214 (1988). https://doi.org/10.1007/BF00174873
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00174873