The Positive Inotropic Action of the Nifedipine Analogue, Bay K 8644, in Guinea-pig and Rat Isolated Cardiac Preparations

Overview

Journal Br J Pharmacol

Publisher Wiley

Specialty Pharmacology

Date 1985 Sep 1

PMID 2413938

Citations 10

Authors

M Finet

T GODFRAIND

G Khoury

Affiliations

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Abstract

The inotropic effect of Bay K 8644 has been studied in rat and guinea-pig atria and ventricular strips stimulated at 1 Hz, in a medium containing CaCl2 1.8 mM. The positive inotropic effect at maximal effective concentrations of Bay K 8644 was in the following order: guinea-pig ventricle greater than rat ventricle greater than guinea-pig atria greater than greater than rat atria. In rat preparations, the tension recorded at maximum effective concentrations of Bay K 8644 was similar at three different calcium concentrations (0.7, 1.8, 3.0 mM). The amplitude of the positive inotropic effect evoked by Bay K 8644 increased when atrial and ventricular contractions were reduced by lowering the external calcium concentration. The contractile tension reached in the presence of maximum effective concentrations of Bay K 8644 (3 X 10(-7) -1 X 10(-6) M) was greater than that produced by the maximum effective concentration of external calcium (3 mM) in rat ventricles but not in rat atria. High doses of nifedipine (3 X 10(-7) -1 X 10(-6) M) depressed the contraction of rat atria more than the contraction of rat ventricles. In rat ventricles, nifedipine shifted to the right the inotropic dose-effect curve of Bay K 8644. It is concluded that the interaction between nifedipine and Bay K 8644 occurred at the same binding sites. These sites have some characteristics of the low affinity binding sites of nifedipine and other related dihydropyridines.

Citing Articles

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Positive inotropic effects of calcium channel antagonists are not necessarily caused by partial calcium channel agonism.

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Stereoisomers of BAY K 8644 show opposite activities in the normal and ischaemic rat heart. A comparison with nifedipine.

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References

Bellemann P, Ferry D, Lubbecke F, Glossman H . [3H]-Nitrendipine, a potent calcium antagonist, binds with high affinity to cardiac membranes. Arzneimittelforschung. 1981; 31(12):2064-7. View

ARUNLAKSHANA O, SCHILD H . Some quantitative uses of drug antagonists. Br J Pharmacol Chemother. 1959; 14(1):48-58. PMC: 1481829. DOI: 10.1111/j.1476-5381.1959.tb00928.x. View

Lee K, Tsien R . Mechanism of calcium channel blockade by verapamil, D600, diltiazem and nitrendipine in single dialysed heart cells. Nature. 1983; 302(5911):790-4. DOI: 10.1038/302790a0. View

Schramm M, Thomas G, Towart R, Franckowiak G . Novel dihydropyridines with positive inotropic action through activation of Ca2+ channels. Nature. 1983; 303(5917):535-7. DOI: 10.1038/303535a0. View

Marsh J, Loh E, Lachance D, Barry W, Smith T . Relationship of binding of a calcium channel blocker to inhibition of contraction in intact cultured embryonic chick ventricular cells. Circ Res. 1983; 53(4):539-43. DOI: 10.1161/01.res.53.4.539. View

Janis R, SCRIABINE A . Sites of action of Ca2+ channel inhibitors. Biochem Pharmacol. 1983; 32(23):3499-507. DOI: 10.1016/0006-2952(83)90295-2. View

Bellemann P . Binding properties of a novel calcium channel activating dihydropyridine in monolayer cultures of beating myocytes. FEBS Lett. 1984; 167(1):88-92. DOI: 10.1016/0014-5793(84)80838-8. View

GODFRAIND T, Finet M, Lima J, Miller R . Contractile activity of human coronary arteries and human myocardium in vitro and their sensitivity to calcium entry blockade by nifedipine. J Pharmacol Exp Ther. 1984; 230(2):514-8. View

Kokubun S, Reuter H . Dihydropyridine derivatives prolong the open state of Ca channels in cultured cardiac cells. Proc Natl Acad Sci U S A. 1984; 81(15):4824-7. PMC: 391583. DOI: 10.1073/pnas.81.15.4824. View

10.

Wahler G, Sperelakis N . New Ca2+ agonist (Bay K 8644) enhances and induces cardiac slow action potentials. Am J Physiol. 1984; 247(2 Pt 2):H337-40. DOI: 10.1152/ajpheart.1984.247.2.H337. View

11.

Sanguinetti M, Kass R . Regulation of cardiac calcium channel current and contractile activity by the dihydropyridine Bay K 8644 is voltage-dependent. J Mol Cell Cardiol. 1984; 16(7):667-70. DOI: 10.1016/s0022-2828(84)80631-8. View

12.

Vaghy P, GRUPP I, GRUPP G, Schwartz A . Effects of Bay k 8644, a dihydropyridine analog, on [3H]nitrendipine binding to canine cardiac sarcolemma and the relationship to a positive inotropic effect. Circ Res. 1984; 55(4):549-53. DOI: 10.1161/01.res.55.4.549. View

13.

Gorman A, Levy S, Nasi E, Tillotson D . Intracellular calcium measured with calcium-sensitive micro-electrodes and Arsenazo III in voltage-clamped Aplysia neurones. J Physiol. 1984; 353:127-42. PMC: 1193298. DOI: 10.1113/jphysiol.1984.sp015327. View

14.

Hess P, Lansman J, Tsien R . Different modes of Ca channel gating behaviour favoured by dihydropyridine Ca agonists and antagonists. Nature. 1984; 311(5986):538-44. DOI: 10.1038/311538a0. View

15.

Bellemann P, Schade A, Towart R . Dihydropyridine receptor in rat brain labeled with [3H]nimodipine. Proc Natl Acad Sci U S A. 1983; 80(8):2356-60. PMC: 393819. DOI: 10.1073/pnas.80.8.2356. View