Vascular effects of betaxolol, a cardioselective beta-adrenoceptor antagonist, in isolated rat arteries.

The effects of betaxolol on isolated rat arteries and the modes of action were investigated. Betaxolol (10(-5)-10(-3) M) relaxed the 80 mM K(+)-induced contraction of aortic strips concentration-dependently. The 50% inhibitory concentration of betaxolol in the K(+)-induced contraction was 3 times higher than that of papaverine and about 3 times lower than that of bunitrolol. The relaxations by betaxolol were also demonstrated in renal, mesenteric and femoral arteries. Betaxolol (3 x 10(-6) M-10(-4) M) produced rightward parallel shifts of the concentration-response curves for Ca2+ in the K(+)-depolarized aortic strips. On the other hand, betaxolol produced downward shifts as well as rightward shifts of the concentration-response curves for norepinephrine, 5-HT and angiotensin II. In K(+)-depolarized aortic strips, the cytosolic Ca2+ concentration measured with a fluorescent indicator, fura-2, was decreased by betaxolol (10(-4) M) almost concomitantly with the loss of tention. An elevation of external Ca2+ from 2.5 mM to 10 mM restored both the cytosolic Ca2+ concentration and tention. The relaxations of arteries induced by betaxolol were not influenced by glybenclamide, methylene blue, indomethacin or removal of the endothelium. These results suggest that betaxolol possesses a direct vasodilating action, and the action may be due to the inhibition of Ca2+ influx across the cell membrane.