Role of alpha 1-adrenoceptors in norepinephrine-induced cardiomyopathy.
This study practically delineated the contribution of alpha-adrenoceptor activation to the pathogenesis of norepinephrine (NE) cardiomyopathy. A total of 64 adult New Zealand white rabbits were used. NE cardiomyopathy was produced in rabbits by a 90-minute intravenous infusion of norepinephrine (2 micrograms/kg/min at infusion rate 0.382 ml/min). Arterial blood pressure and heart rate were constantly monitored. Arterial blood samples were obtained at 30-minute intervals for measurements of pH, blood gases, and glucose. Alpha-adrenoceptor blocking agents, when employed, were given 15 minutes prior to the initiation of NE infusion. Two days after treatment the rabbits were killed. The hearts were examined microscopically and assigned a histologic score. Pretreatment with the alpha 1-adrenoceptor blocker prazosin at 50, 100, or 200 micrograms/kg significantly reduced NE-induced myocardial injury in a dose-related manner. In contrast, the presence of alpha 2-adrenoceptor blocker yohimbine at 2.5 or 5.0 mg/kg was ineffective in preventing the formation of myocardial lesions. These findings suggest that NE cardiomyopathy may result largely from activation of the alpha 1-adrenoceptor system in the rabbit model.
D000818:Animals; D001786:Blood Glucose; D001794:Blood Pressure / Q000187:drug effects; D009202:Cardiomyopathies / Q000139:chemically induced* / Q000209:etiology / Q000473:pathology; D006339:Heart Rate / Q000187:drug effects; D009638:Norepinephrine; D011224:Prazosin / Q000494:pharmacology; D011817:Rabbits; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D015016:Yohimbine / Q000494:pharmacology
D001786:Blood Glucose; D011942:Receptors, Adrenergic, alpha; D015016:Yohimbine; D009638:Norepinephrine; D011224:Prazosin