Abstract

Cats were given 6-hydroxydopamine (6-OH-DA; 2,4,5-trihydroxyphenethylamine) i.v. according to a schedule which had previously been found to produce a selective and almost complete destruction of peripheral adrenergic nerve terminals. After varying intervals, spinal preparations, as well as the isolated medial smooth muscle of the nictitating membrane and the isolated perfused heart, were used to study the 6-OH-DA-induced alterations of the effects of sympathetic nerve stimulation and of the sensitivity to norepinephrine. Twelve to 16 days after 6-OH-DA, the norepinephnine content of heart, spleen, nictitating membrane and iris was below 10% of the normal value. At this time, the effects of sympathetic nerve stimulation on the nictitating membrane and heart were strongly reduced. Surgical denervation was somewhat more effective than 6-OH-DA on the nictitating membrane. After both chemical and surgical sympathectomy, the sensitivity to norepinephrine of the isolated nictitating membrane had increased approximately 100-fold; both procedures seem to have induced the presynaptic as well as the postsynaptic types of supersensitivity. Only a 3-fold increase in the sensitivity to norepinephrine was observed in the isolated heart, and evidence was obtained for the absence of the postsynaptic type of supersensitivity in this organ. The damage to the adrenergic nerve terminals caused by 6-OH-DA was reversible; 3 to 4 weeks after chemical sympathectomy, there was a distinct increase in the norepinephrine content of the organs investigated, and after 14 weeks norepinephrine levels were normal again. The effectiveness of sympathetic nerve stimulation also returned gradually, but more rapidly than the levels of tissue norepinephrine.