Use of acute phenolic denervation to show the neuronal dependence of Ca2+-induced relaxation of isolated arteries

We recently showed that perivascular sensory nerves of mesenteric resistanc e arteries (MRA) express a receptor for extracellular Ca2+ (CaR) and propos ed that activation of the CaR by Ca2+ causes nerve-dependent vascular relax ation. We now describe a novel procedure for acutely denervating isolated a rteries and have used this method to test the hypothesis that Ca2+-induced relaxation of MRA is nerve dependent. MRA were studied using a wire myograp h equipped with electrodes for electrical field stimulation (EFS) which cau sed sympathetic nerve-mediated contraction, and when applied in the presenc e of guanethidine, induced nerve-mediated relaxation. Ca2+-induced relaxati on was produced by the cumulative addition of Ca2+ to MRA precontracted wit h norepinephrine. Exposure of MRA to 6.5% phenol in ethanol for 20 sec sign ificantly attenuated EFS-induced contraction and relaxation, and Ca2+-induc ed relaxation. The magnitude of the relaxation response to EFS correlated s ignificantly with the decrease in Ca2+-induced relaxation. In contrast, end othelium-dependent relaxation induced by acetylcholine was slightly, but no nsignificantly decreased by phenol treatment and did not correlate with Ca2 +-induced relaxation. These data indicate that brief exposure of isolated M RA to phenol significantly impairs perivascular nerve function and support the hypothesis that Ca2+-induced relaxation is neurally mediated.