The mechanisms of the inotropic and chronotropic actions of hydralazine on rat isolated atria.
The effects of hydralazine on rat isolated atria depend on its concentration. A negative chronotropic effect due to inhibition of spontaneous release of noradrenaline was produced by concentrations of 1 x 10(-5) - 1 x 10(-4) M, but with concentrations of 2 x 10(-4) M or more the negative chronotropic effect was due to a more direct depression of pacemaker activity. A positive chronotropic effect due to release of noradrenaline was produced by a concentration of 2 x 10(-3) M; when this was abolished by reserpine pretreatment or beta-adrenoceptor blockade, the negative chronotropic effect was unmasked or accentuated. A positive inotropic effect was produced by concentrations of 6 x 10(-4) - 2 x 10(-3) M; this effect was not reduced by reserpine or beta-adrenoceptor blockade, but it was absent in a calcium-free medium and was blocked by verapamil.
D000818:Animals; D002118:Calcium / Q000502:physiology; D005260:Female; D006339:Heart Rate / Q000187:drug effects*; D006632:Histamine / Q000494:pharmacology; D006830:Hydralazine / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D006830:Hydralazine; D006632:Histamine; D002118:Calcium; D009638:Norepinephrine