ISSN:
1432-1912
Keywords:
Calcium antagonists
;
α-Adrenoceptors
;
β-Adrenoceptors
;
Positive inotropic effect
;
Rabbit ventricular myocardium
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Summary Experiments were carried out to elucidate the mechanism that the positive inotropic effect mediated by α1-adrenoceptors is more susceptible to organic calcium antagonists than the β-adrenoceptor-mediated effect. Verapamil and diltiazem displaced the specific binding of [3H]prazosin to the membrane fraction derived from the rabbit ventricular myocardium, verapamil being about 70 times more potent than diltiazem. Nifedipine did not displace the binding. While these compounds suppressed the positive inotropic effect mediated via αl-adrenoceptors in α1- concentration-dependent manner, there was no correlation between the potency of the compounds to displace the [3H]prazosin binding and to inhibit the α-mediated positive inotropic effect. The relative potency of three calcium antagonists to decrease the basal force of contraction and the al-mediated effect (of the same extent as compared to basal force of contraction) was consistent to each other. The positive inotropic effect mediated by β-adrenoceptors was inhibited much less, and was enhanced by low concentrations of organic calcium antagonists. The differential action of calcium antagonists on the α- and β-mediated positive inotropic effect was mimicked by lowering the extracellular calcium concentration to 1/2, 1/4 and 1/8 of that in normal Krebs-Henseleit solution (2.5 mmol/l). These results indicate that the α1-adrenoceptor blocking activity does not play an essential role for the preferential inhibition of α-mediated positive inotropic effect by organic calcium antagonists. Difference in the subcellular mechanism involved in mobilization of intracellular Ca2+ subsequent to α1-and β-adrenoceptor activation may be responsible for the differential inhibitory action of calcium antagonists in the rabbit heart.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00169732
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