The role of the endothelium on calcium-entry blockade in coronary vasospasm.

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Calcium-entry blockers are widely used for the treatment of coronary vasospasm. The mechanisms responsible for coronary vasospasm are still uncertain, but ultimately involve contraction of the vascular smooth muscle of the large coronary artery. The direct constrictor responses of coronary smooth muscle can be reduced by the inhibitory effect of endothelium-derived relaxing factor(s). The absence of endothelium can augment the response of vascular smooth muscle to vasoconstrictor stimuli, but may also modify the potency of calcium-entry blockers. The role of calcium-entry blockers on the endothelial function is not known. Nisoldipine is a new compound from a series of calcium-antagonistic dihydropyridines. The aim of the present experiments was: 1. to determine the effect of nisoldipine on contractions of large coronary arteries evoked by possible mediators of coronary vasospasm and 2. to determine whether or not the presence of endothelial cells affects the response to the calcium-entry blockers. Rings of canine coronary arteries with and without endothelium were studied in organ chambers filled with modified Krebs-Ringer bicarbonate solution. The rings were incubated for 45 min either in control solution or in the presence of increasing concentrations of nisoldipine (10(-10) to 10(-6) M). In the concentration range of 10(-9) to 10(-7) M nisoldipine inhibited the contractile responses evoked by allagents: KCL (10 to 80 mM), 5-hydroxytryptamine (10(-9) to 10(-6) M), ergonovine (10(-9) to 10(-6) M), norepinephrine and phenylephrine (10(-9) to 10(-4) M both in the presence of propranolol 5 X 10(-6) M). Nisoldipine was more potent in inhibiting contractions to potassium chloride in the absence of the endothelium. By contrast, in case of 5-hydroxytryptamine or phenylephrine, nisoldipine was less potent in the absence of the endothelium. Similar results were obtained in the case of ergonovine and norepinephrine. The hypoxic contractions were reduced by nisoldipine in a concentration dependent manner. Nisoldipine inhibited the platelet-induced contractions both in the presence and the absence of endothelium. The present study demonstrates that the dihydropyridine, nisoldipine, is a potent inhibitor of contractions of the smooth muscle of large coronary arteries caused by a number of putative mediators of coronary vasospasm including catecholamines and products released by aggregating platelets. It also prevents hypoxic contractions of coronary vascular smooth muscle.

Original languageEnglish (US)
Pages (from-to)295-313
Number of pages19
JournalVerhandelingen - Koninklijke Academie voor Geneeskunde van Belgie
Issue number4
StatePublished - Dec 1 1989

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