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. KEY WORDSadrenergic nerve terminals heart rate blood pressure endogenous norepinephrine tyramine right stellate ganglion stimulation adrenal glands• Sympathectomy has been frequently used to investigate the role of the sympathetic nervous system. However, surgical denervation is not specific, is usually limited to individual organs, and often requires extensive surgery and high degrees of technical skill. On the other hand, norepinephrine-depleting

Fetal Cardiovascular and Catecholamine Responses to Hypoxemia after Chemical Sympathectomy

“…Surgical sympathectomy has serous limitations because it often requires extensive surgical manipulation and is usually limited to individual organs. Drugs that deplete norepinephrine, such as reserpine, have the disadvantage of interfering with functions unrelated to the sympathetic nervous system (9). The synthetic catecholamine, 6HD, is closely related to the naturally occurring neurotransmitters and has been shown to produce prolonged depletion of NE from postganglionic sympathetic nerve terminals by altering the binding sites (21).…”

“…Cumulative doses of 50 mg/kg of 6HD have been used in dogs to achieve complete sympathectomy (9,20); however, intravenous infusion of 5% Dextran has been necessary to maintain adequate plasma volume and present circulatory collapse during these acute studies in which the 6HD was administered over 4-10 h. The rapid decrease in plasma volume was attributed to the very high levels of circulating catecholamines released by 6HD (9). We have attempted to minimize the acute effect of 6HD on blood volume by infusing progressively larger doses over 5 d until a total of 60-70 mg/kg was reached.…”

“…A supplemental dose of 20 mg/kg was given every 7-10 d thereafter in order to insure continuation of effective sympathectomy. The adequacy of sympathectomy was evaluated by the intravenous administration of tyramine (100-400 pglkg) before and after completion of the 6HD dose schedule (9). The hematocrit was measured before and after each daily dose for the first three animals in order to determine whether hemoconcentration had occurred (9).…”

“…The adequacy of sympathectomy was evaluated by the intravenous administration of tyramine (100-400 pglkg) before and after completion of the 6HD dose schedule (9). The hematocrit was measured before and after each daily dose for the first three animals in order to determine whether hemoconcentration had occurred (9). Because no change in hematocrit was observed, this measurement was discontinued for the remainder of the study group.…”

Effect of 6-Hydroxydopamine on Cardiotoxicity of Ouabain in Guinea Pigs

“…It has already been shown that systemic administration of 6-hydroxydopamine in duced a selective reduction of catecholamines in the peripheral tissues without any signifi cant alteration of the catecholamine content in the brain (6,7,8). Under these same ex perinmental conditions, we also determined the catecholamine content of brain cortex, brain stem, heart and adrenal glands.…”