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ABSTRACT-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 contrac tion 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 106 M 10-4 M) produced rightward parallel shifts of the concentration-response curves for Ca 2+ 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 cyto solic Ca 2+ 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 Ca 2+ 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 Ca 2+ influx across the cell membrane. Betaxolol [(±)-1-[4-[2-(cyclopropylmethoxy) ethyl]phenoxy]-3-(isopropylamino)-2-propanol]hydrochloride is a cardioselective ,Q-adreno ceptor antagonist with no intrinsic sympatho mimetic activity and little membrane stabiliz ing activity (1, 2). In patients with essential hypertension, betaxolol was shown to produce potent and long lasting antihypertensive effects by once daily therapy (2, 3) because of high bioavailability and a long elimination half life (4, 5).In previous laboratory studies, we (6-8) and other workers (9) have shown that a single oral administration of betaxolol lowers the blood pressure of various hypertensive models, i.e., spontaneously hypertensive rats, renal hypertensive rats, deoxycorticosterone/ saline hypertensive rats and renal hypertensive dogs. However, other 8-adrenoceptor anta gonists such as atenolol are unlikely to pro duce antihypertensive effects by single admin istration in these hypertensive models (10 13). These data suggest that betaxolol might have a certain effect other than 8-adreno ceptor antagonism. In fact, betaxolol induced an increase in blood flow by intraarterial administration (6) and a decrease in total peripheral resistance by intravenous adminis tration in anesthetized dogs (14).Although / -adrenoceptor antagonism of be taxolol has been well studied (2), the effects of betaxolol on isolated arteries have not yet

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