Neurogenic Histaminergic Vasodilation in Canine Skeletal Muscle: Mediation by c^-Adrenoceptor Stimulation

This study examines the neurogenic effect of a2-adrenoceptor stimulation on skeletal muscle vascular resistance and its relation to the level of background sympathetic activity. The isolated, separately perfused, neurally intact canine gracilis muscle preparation was used since it permits deliberate and quantifiable alterations in background sympathetic activity, as measured by skeletal muscle vascular resistance. Systemic intravenous UK-14304, a highly selective a,-adrenoceptor agonist, produced a precipitous, neurogenic vasodilation that lowered vascular resistance below the subsequently denervated resistance, thus indicating that an active vasodilation was involved. The overall magnitude of the vasodilation was much greater in animals that had been hemorrhaged to elevate background sympathetic activity than in animals that had been transfused to lower background activity. The neurogenic vasodilation was unaffected by baroreceptor and cardiopulmonary receptor denervation and by prior cholinergic-receptor blockade of the gracilis muscle. Prior H,and H,-histaminergic-receptor blockade, on the other hand, eliminated the active vasodilation but not a vasodilation down to the subsequently denervated resistance. Prior a,-adrenoceptor blockade lowered resistance down to the subsequently denervated resistance and greatly attenuated the active vasodilation. The present study demonstrates that withdrawal of sympathetic activity by ct2-adrenoceptor stimulation produces an active vasodilation resulting from histamine release in skeletal muscle as well as a passive vasodilation resulting from lysis of peripheral vasoconstrictor tone. (Circulation Research 1988; 62:871-883)