The effect of chemical denervation on the action of acetylcholine and substance P in the isolated perfused mesenteric arterial bed of the rat

Abstract

Vascular endothelial cells respond to certain vasoactive agents by releasing factors which act on medial smooth muscle to cause relaxation or contraction of blood vessels. One of the substances responsible for endothelium-dependent relaxation to acetylcholine has recently been identified as nitric oxide. We have tested the hypothesis that the ability of vascular endothelium to cause relaxation in response to stimulation by vasoactive agents is related in some way to the pattern of perivascular innervation. The actions of acetylcholine and substance P were tested in the presence of methoxamine induced tone in the isolated perfused mesenteric arterial bed of the rat. Tissues were tested from untreated normal 12 week old Sprague-Dawley rats and from rats which had been treated from birth with capsaicin to prevent the development of peptidergic perivascular innervation or 6-hydroxydopamine to prevent development of catecholaminergic innervation. Concentration dependent endothelium-dependent relaxations were observed in response to acetylcholine. The concentration response curve to acetylcholine was shifted 1.2 log units to the right in the capsaicin-treated group but no change was observed with 6-hydroxydopamine treatment. Substance P caused a dose dependent potentiation of the methoxamine induced tone which was not dependent on the presence of an intact endothelium. Relaxations to substance P were not observed at any dose. Sympathectomy with neonatal 6-OHDA treatment resulted in an increase in the substance P pressor response, but no changes were observed with capsaicin treatment. Thus, it appears that altering the peptidergic perivascular innervations results in a decreased sensitivity of the mesenteric arterial bed to acetylcholine and changes in the catecholaminergic fibre plexus result in an enhancement of the substance P modulation of adrenergic vasoconstriction.