It was the aim of the present study to gain more insight into the role of calcium from both extracellular and intracellular sources in the regulation of coronary arterial tone. The effects of verapamil, nifedipine and diltiazem on the cardiac
function,
especially in coronary flow rate were compared in the isolated working rat heart. also the influences of these drugs on the effects of phenylephrine (PE), clonidine and methacholine(MCh) which were well known as coronary spasmogens, were
investigated.
When introduced into the left atrium, verapamil, a Ca2+-channedl blocker in doses of 10-7-10-5M decreased heart rate and coronary flow rate. The moderate doses of other types of Ca2+-antagoinsts, nicardipine(10-7-10-6M) and diltiazem(10-7-10-5M),
decreased the coronary arterial resistance and increased the coronary flow with dose-dependent manner, with diltiazem having more potent than nicardipine. The adrenergic agents, phenylephrine(10-4M) and clonidine(10-4M). as well as the
parasympathomimetics methacholine(10-5M) increased coronary arterial resistance and decreased coronary flow rate, and the effects produced by phenylephrine and clonidine were blocked by Ca++-entry blockers. However, the effect of methacholine was
blocked by nicardipine but not by verapamil and diltiazem. Bay K 8644, a calcium-channel agonist, increased coronary arterial resistance and decreased coronary flow rate, and the effects of silmultaneous administration of Bay K 8644(10-5M) and
phenylephrine(10-4M) were much greater than those of single agents. Bay K 8644 inhibited the effect of nicardipine(10-7M) but not that of diltiazem(10-7M).
From these resutls, it is suggested that the decreases of the coronary flow by phenylephrine and clonidine are due to coronary vasoconstriction which is caused by extracellular Ca++ influx. However, the methacholine-induced contriction is not
related to
the Ca2+ influx. It is thus concluded that the constriction of coronary vessel caused byactivation of symphathetic nervous system is blocked by Ca+ entry blockers, whereas the effect caused by activation of parasympathetic nervous system is not
susceptible to Ca+ entry blockade, but blocked by nicardipine.
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