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.
Pharmaceuticals Laboratory, Mitsubishi Kasei Corporation, Yokohama, Japan.
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H
Bessho
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Suzuki
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Tobe
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001158:Arteries / Q000187:drug effects; D015784:Betaxolol / Q000494:pharmacology*; D015740:Calcitonin Gene-Related Peptide / Q000502:physiology; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D006152:Cyclic GMP / Q000502:physiology; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects; D011453:Prostaglandins / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000494:pharmacology
D000319:Adrenergic beta-Antagonists; D015221:Potassium Channels; D011453:Prostaglandins; D000804:Angiotensin II; D012701:Serotonin; D006152:Cyclic GMP; D015740:Calcitonin Gene-Related Peptide; D015784:Betaxolol; D011188:Potassium; D002118:Calcium; D009638:Norepinephrine