PMID: 6168842May 1, 1981Paper

Myocardial sensitivity to isoproterenol following abrupt propranolol withdrawal in conscious dogs

Journal of Cardiovascular Pharmacology
J G WebbH B Daniell

Abstract

The sensitivity of the cardiovascular system to isoproterenol following abrupt cessation of propranolol administration was studied in chronically instrumented conscious dogs pretreated orally with propranolol for 14 days. The effects of intravenous isoproterenol on heart rate, blood pressure, and mean velocity of circumferential fiber shortening (Vcf) were determined before and during propranolol administration and then at 12 hr intervals following drug withdrawal. During propranolol administration, all dose-response curves to isoproterenol were predictably shifted to the right. Twenty-four hours following propranolol withdrawal, when plasma levels of drug averaged only 7 ng/ml, the chronotropic response to isoproterenol remained significantly inhibited. In contrast, the Vcf response recovered rapidly and at 24 hr equaled the pretreatment control response. Furthermore, between 36 and 60 hr, when plasma propranolol levels averaged less than 1 ng/ml, the Vcf dose-response curve to isoproterenol was shifted to the left of control prior to returning to the pretreatment level. This leftward displacement of the Vcf response curve was not accompanied by a parallel change in the heart rate response or in afterload. Plasma norepinephrin...Continue Reading

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