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 resistance arteries (MRA) express a receptor for extracellular Ca2+ (CaR) and proposed that activation of the CaR by Ca2+ causes nerve-dependent vascular relaxation. We now describe a novel procedure for acutely denervating isolated arteries and have used this method to test the hypothesis that Ca2+-induced relaxation of MRA is nerve dependent. MRA were studied using a wire myograph equipped with electrodes for electrical field stimulation (EFS) which caused sympathetic nerve-mediated contraction, and when applied in the presence of guanethidine, induced nerve-mediated relaxation. Ca2+-induced relaxation was produced by the cumulative addition of Ca2+ to MRA precontracted with norepinephrine. Exposure of MRA to 6.5% phenol in ethanol for 20 sec significantly attenuated EFS-induced contraction and relaxation, and Ca2+-induced relaxation. The magnitude of the relaxation response to EFS correlated significantly with the decrease in Ca2+-induced relaxation. In contrast, endothelium-dependent relaxation induced by acetylcholine was slightly, but nonsignificantly decreased by phenol treatment and did not correlate with Ca2+-induced relaxation. These data indicate that brief exposure of isolated MRA to phenol significantly impairs perivascular nerve function and support the hypothesis that Ca2+-induced relaxation is neurally mediated.
Wang
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Department of Internal Medicine, University of Texas Medical Branch, Galveston Island 77555-1065, USA.
Bukoski
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D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D002135:Calcium-Binding Proteins / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D004730:Endothelium, Vascular / Q000187:drug effects / Q000294:innervation / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000294:innervation* / Q000502:physiology; D009119:Muscle Contraction / Q000187:drug effects; D009121:Muscle Denervation; D009126:Muscle Relaxation / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000294:innervation* / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009638:Norepinephrine / Q000494:pharmacology; D019800:Phenol / Q000494:pharmacology*; D010646:Phentolamine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013779:Tetrodotoxin / Q000494:pharmacology; D014666:Vasomotor System / Q000502:physiology*
D002135:Calcium-Binding Proteins; D019800:Phenol; D013779:Tetrodotoxin; D000109:Acetylcholine; D002118:Calcium; D009638:Norepinephrine; D010646:Phentolamine