The involvement of CGRP in acetylcholine-induced vascular relaxation.
Earlier work on peptidergic fibres suggested some involvement of CGRP perivascular nerve fibres in acetylcholine-induced endothelium-dependent vascular relaxation. We have investigated the effect of blocking CGRP receptors and CGRP replacement on acetylcholine-induced endothelium-dependent vascular relaxation in the isolated perfused mesenteric arterial bed in normal Sprague-Dawley rats and in rats seven days following freeze-denervation of the superior mesenteric artery. Freeze-denervation was carried out under pentobarbital anesthesia (40 mg/Kg). It was found that the ability of acetylcholine to cause relaxation was reduced by CGRP receptor blocking with CGRP8-37 in vessels from control rats, but returned to pre-blocking levels after washout of the antagonist. Treatment with CGRP increased the relaxation due to acetylcholine in denervated vessel beds, but not in control tissues. The CGRP receptor appears to be involved in the acetylcholine-induced relaxation of blood vessels. The mechanism of action is not known, although both acetylcholine and CGRP, act through activation of K+ channels, and CGRP may facilitate the activation of K+ channels by acetylcholine.
Faculty of Medicine, Memorial University of Newfoundland, St. John's, Canada.
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D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology / Q000502:physiology*; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D000242:Cyclic AMP / Q000502:physiology; D003714:Denervation; D004357:Drug Synergism; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D005615:Freezing; D017538:Mesenteric Artery, Superior / Q000187:drug effects / Q000294:innervation; D009419:Nerve Tissue Proteins / Q000502:physiology*; D010446:Peptide Fragments / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; D015221:Potassium Channels; C058636:calcitonin gene-related peptide (8-37); D000242:Cyclic AMP; D015740:Calcitonin Gene-Related Peptide; D000109:Acetylcholine