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  • Title: Features of the acute hypotensive action of carvedilol and its ameliorating effect on myocardial ischemia.
    Author: Hashimoto H, Kanda A, Hubo H, Tanaka M.
    Journal: J Cardiovasc Pharmacol; 1991; 18 Suppl 4():S22-8. PubMed ID: 1721975.
    Abstract:
    The objective of the present experiment was to investigate the following parameters concerning carvedilol: (a) the time course of acute hypotensive effect, (b) the influence of alpha 1-adrenoceptor blockade on the acute hypotension induced by carvedilol, and (c) the effect of carvedilol on myocardial ischemia. In conscious, catheter-implanted spontaneously hypertensive rats, carvedilol at the doses of 10 and 30 mg/kg, p.o., dose-dependently decreased mean arterial blood pressure (MAP). At 10 mg/kg, MAP was significantly decreased for 16 h, and at 30 mg/kg, it was significantly decreased until 24 h after administration. Thus, carvedilol shows long-lasting antihypertensive effects by a single oral administration. In anesthetized Wistar rats, intravenous administration of carvedilol (0.3 mg/kg) produced an immediate decrease in blood pressure. On the other hand, in phentolamine-pretreated rats whose blood pressure was restored by prostaglandin F2 alpha, the acute hypotension produced by carvedilol was abolished similarly to the case with labetalol (0.6 mg/kg) and prazosin (0.01 mg/kg). The hypotensive effect of either hydralazine (0.2 mg/kg) or nitroprusside Na (0.005 mg/kg) was attenuated by about 20%, whereas the effect of diltiazem (0.2 mg/kg) was not attenuated. These results indicate that alpha 1-adrenoceptor blocking action of carvedilol contributes to a large extent to the acute hypotensive effect of this drug. In anesthetized open-chest dogs, myocardial ischemia was produced by partial occlusion of the left anterior descending coronary artery. Myocardial pH of the ischemic region was decreased by about 0.7 units. Carvedilol at the doses of 0.1 and 0.3 mg/kg, i.v., dose-dependently attenuated the decrease in myocardial pH accompanied with decreases in MAP and heart rate.(ABSTRACT TRUNCATED AT 250 WORDS)
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