Characterization of alpha adrenoceptors on vascular smooth muscle: electrophysiological differentiation in canine saphenous vein

Abstract

The effects of selective alpha adrenoceptor agonists on resting transmembrane potential (Em) and contractile responses of vascular smooth muscle of the canine saphenous vein (CSV) were investigated using microelectrode and isometric tension recording techniques. The Em of the smooth muscle cells of the CSV was -59.5 mV +/- 0.3 (mean +/- S.E., n = 363). The cells were electrically quiescent and did not show spontaneous electrical activity. Norepinephrine (a mixed alpha-1/alpha-2 adrenoceptor agonist), applied in concentrations of 1 X 10(-9) to 1 X 10(-7) M did not depolarize the CSV cell membrane. However, 50% of the maximum contractile response to norepinephrine occurred over this concentration range. At concentrations greater than 1 X 10(-7) M, a dose-dependent contraction and depolarization was observed with norepinephrine. The contractile and depolarization effects of norepinephrine were antagonized by the selective alpha-1 antagonist, prazosin. The selective alpha-1 agonists methoxamine and SK&F l-89748 (l-[1,2,3,4-tetrahydro-8-methoxy-5-(methylthio)-2-naphthalenamine] ) caused a dose-dependent depolarization and contraction of the CSV. In contrast, the alpha-2 adrenoceptor agonists, BHT-920 and M-7, could be distinguished from the alpha-1 adrenoceptor agonists by their lack of effect on Em. M-7, at concentrations up to 1 X 10(-6) M, failed to produce a depolarization; however, at 10(-6) M, M-7 produced 80% of its maximum contractile response.(ABSTRACT TRUNCATED AT 250 WORDS)