Acute and Chronic Cardiovascular Effects of 6-Hydroxydopamine in Dogs

Abstract

Acute and chronic cardiovascular effects of repeated injections of 6-hydroxydopamine were studied in unanesthetized dogs. The acute response to initial injections of small doses of 6-hydroxydopamine consisted of an intense sympathomimetic effect characterized by a marked increase in blood pressure and a reflex bradycardia. Three days after the administration of a total dose of 50 mg/kg of 6-hydroxydopamine, significant decreases in heart rate, blood pressure, and total peripheral resistance were observed, but cardiac output remained unchanged. The absence of a response to intravenously injected tyramine, to electrical stimulation of the right stellate ganglion, and to bilateral carotid occlusion was consistent with a state of complete peripheral sympathectomy. Along with the functional impairment of transmission at the sympathetic nerve endings, marked endogenous norepinephrine depletion was observed in the heart, carotid sinus, and spleen. In contrast, endogenous norepinephrine was increased in the stellate ganglion. The response to electrical stimulation of the distal end of the right vagus was not altered by treatment with 6-hydroxydopamine. In anesthetized dogs treated with 6-hydroxydopamine, clamping of the hilar vessels of the adrenal glands for 10 minutes caused hypotension, but the same procedure in normal dogs did not affect blood pressure, demonstrating the importance of the compensatory role of the adrenal medulla in sympathectomized animals. It is concluded that 6-hydroxydopamine can be used effectively to obtain a generalized chemical sympathectomy in unanesthetized dogs and provides a useful means for studying the role of the autonomic nervous system in the regulation of cardiovascular functions.