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The Vasorelaxing Effect of CGRP and Natriuretic Peptides in Isolated Bovine Retinal Arteries

From the Department of Physiology and Pathophysiology, Ghent University, Belgium.

PURPOSE. To study the vasorelaxing effect of calcitonin gene-related peptide (CGRP) and natriuretic peptides on isolated bovine retinal arteries (BRAs) and to evaluate the possibility of the unidentified retinal relaxing factor (RRF) being one of these peptides.

METHODS. Retinal arteries were isolated from bovine eyes and mounted in a wire myograph for isometric tension recording. Concentration–response curves were generated by cumulative addition of the peptides to the organ bath.

RESULTS. In BRAs, CGRP-induced relaxation was significantly reduced by removal of the endothelium or by application of the nitric oxide synthase (NOS) inhibitor N-nitro-L-arginine (L-NA) or the soluble guanylyl cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ). The nonselective K⁺ channel blocker tetraethylammoniumchloride (TEA) and the voltage-dependent K⁺ channel blocker 4-aminopyridine significantly reduced the CGRP response, whereas the Ca²⁺ activated K⁺ channel blockers apamin plus charybdotoxin, the inward rectifier K⁺ channel blocker Ba²⁺, and the adenosine triphosphate (ATP)-sensitive K⁺ channel blocker glibenclamide had no effect. The CGRP receptor antagonist CGRP 8-37 caused a small, but not significant, rightward shift in the concentration–response curve for CGRP, whereas the AM-receptor antagonist AM 22-52 had no effect. The natriuretic peptides did not induce relaxation in isolated retinal arteries.

CONCLUSIONS. Endothelium-derived NO, voltage-dependent K⁺ channels, and possibly also CGRP₁ receptors are involved in the CGRP response in BRAs. The natriuretic peptides do not induce vasorelaxation in isolated BRAs. No evidence was found that CGRP or a natriuretic peptide is the as yet unidentified RRF.

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