Effect of chronic sensory denervation on Ca(2+)-induced relaxation of isolated mesenteric resistance arteries

Abstract

We recently reported that Ca(2+)-induced relaxation could be linked to a Ca2+ receptor (CaR) present in perivascular nerves. The present study assessed the effect of chronic sensory denervation on Ca(2+)-induced relaxation. Mesenteric resistance arteries were isolated from rats treated as neonates with capsaicin (50 mg/kg), vehicle, or saline. The effect of cumulative addition of Ca2+ was assessed in vessels precontracted with 5 microM norepinephrine. Immunocytochemical studies showed that capsaicin treatment significantly reduced the density of nerves staining positively for calcitonin gene-related peptide (CGRP) and for the CaR (CGRP density: control, 51.1 +/- 3.9 microns2/mm2; capsaicin treated, 31.4 +/- 2.8 microns2/mm2, P = 0.01; control CaR density, 46 +/- 4 microns2/mm2, n = 7; capsaicin-treated CaR density, 24 +/- 4 microns2/mm2, n = 8, P = 0.002). Dose-dependent relaxation to Ca2+ (1-5 mM) was significantly depressed in vessels from capsaicin-treated rats (overall P < 0.001, n = 6 or 7), whereas the relaxation response to acetylcholine remained intact. These data support the hypothesis that Ca(2+)-induced relaxation is mediated by activation of the CaR associated with capsaicin-sensitive perivascular neurons.