아데노신의 혈관 평활근에 대한 작용기전

Abstract

Adenosine, a potent coronary vasodilator. has been known to be endogenously formed and released from the rnyocardiac cells and to induce coronary vasodilation when the oxygen supply to the myocardium is reduced. However, the mechanism of adenosine-induced relaxation of coronary vascular smooth muscle has not yet been clarified. The inhibitory mechanisms of adenosine on the activated strips by electrical field stimulation, high K·Tyrode solution, or acetylcholine were studied in isolated pig coronary artery. Helical strips of arterial muscle were prepared from the extramural and intramural coronary artery of pigs. All experiments were performed in HC03--buffered Tyrode solution which was aerated with 396 CO2- 9796 O2 mixed gas and kept at 35'C. The phasic contractions induced by electrical field stimulation CA.C" 60Hz, 5V /cm, duration 15 sec, period 3 min) were suppressed by the addition of adenosine. Both passive resting tension and active tension were rapidly decreased after the addition of adenosine to bathing Tyrode solution, but the active phasic contractions were gradually recovered from the adenosine'induced depression of contractility. Adenosine did not exhibit tachyphylaxis. Adenosine also suppressed K-contractures in a dose-dependent manner, which were developed mainly by the increase of Ca influx. This inhibitory action of adenosine on K-contracture was more potent and preferentially in small intramural coronary strips than in large extramural coronary strips, and was inversely related to the degree of membrane depolarization. Differential effects of adenosine on the relaxing responses of large and small coronary arteries suggest the possibility of an existence of a surface adenosine receptor on coronay myocytes. The component of contraction curve, associated with the release of bound Ca and induced by ace' tylcholine, was obviously suppressed by the adminis· tration of adenosine. The results of this experiment suggest that the adenosine-induced relaxation of coronary vascular smooth muscle was developed by inhibiting trans' membrane Ca influx and/or interfering intracellular release of Ca.