INFLUENCE OF THE ENDOTHELIUM ON TONE AND THE RESPONSE OF ISOLATED PIG CORONARY-ARTERY TO NOREPINEPHRINE

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  • 1 February 1988
    • journal article
    • research article
    • Vol. 244  (2) , 550-555
Abstract
The influence of the endothelium on smooth muscle tone and the response of the pig right coronary artery to norepinephrine (NE) was studied. Isolated rings of artery with and without endothelium were stretched in the presence of nitroprusside to a tension previously determined to be optimal for contraction. During wash out of the nitroprusside, rings without endothelium spontaneously generated tone representing 24% of the contraction caused by potassium (120 mM); in rings with endothelium no significant spontaneous tone was observed. Relaxations were caused by NE in rings with endothelium contracted with prostaglandin F2.alpha. (PGF2.alpha.). In rings without endothelium, NE relaxed spontaneously generated tone as well as that produced by PGF2.alpha.. Independent of the mode or degree of contraction, rings with endothelium were more sensitive to NE than rings without endothelium. The difference in sensitivity to NE between rings with and without endothelium was likely due to endothelial cell alpha-2 adrenoceptors, inasmuch as the difference was abolished by rauwolscine. In the presence of propranolol and prazosin, endothelium-dependent relaxations were observed which were also inhibited by rauwolscine. Nevertheless, beta adrenoceptors are the predominant mediator of the relaxation to NE of pig coronary smooth muscle, because propranolol caused a greater shift to the right of the relaxation induced by NE compared to that caused by endothelium removal. Accordingly, under resting conditions, NE caused contractions only in the presence of propranolol. These contractions were attenuated by prazosin or rawwolscine, but blocked only by a combination of both alpha adrenoceptor antagonists. Thus, the response of pig coronary artery smooth muscle to NE is mediated by smooth muscle beta-, alpha-1 and alpha-2 adrenoceptors as well as alpha-2 adrenoceptors on endothelial cells. The endothelium nearly prevented contractions caused by NE, and inhibited spontaneously developed tone and PGF2.alpha.-induced contractions. Because the endothelium inhibited with equal effectiveness the contractions caused by NE in the presence of rauwolscine or prazosin, the mechanism of inhibition was not primarily by way of endothelial cell alpha-2 adrenoceptor stimulation. Furthermore, in perfusion-cascade experiments the perfusate of coronary artery segments with endothelium contained vasodilators which markedly relaxed an assay ring without endothelium contracted by PGF2.alpha.. These observations suggest that an important mechanism by which the endothelium inhibits contractions of the pig coronary artery is via spontaneously released vasodilators.