Endothelium and the vasodilator action of rat calcitonin gene‐related peptide (CGRP)

Abstract

1 Acetylcholine and rat calcitonin gene-related peptide (CGRP) produced a relaxation in rat isolated aortic rings which was entirely dependent on the presence of the endothelium. 2 In the absence of any exogenous vasodilator agent, the cyclic guanosine monophosphate (cyclic GMP) content was higher in rings with endothelium than in those without. 3 The vasorelaxation produced by acetylcholine and sodium nitroprusside was accompanied by increases in cyclic GMP in the smooth muscle, whereas that produced by CGRP was not accompanied by cyclic GMP accumulation. 4 Therefore, it appears unlikely that CGRP releases an endothelium-derived relaxing factor similar to that released by acetylcholine.

Human α‐calcitonin gene‐related peptide stimulates adenylate cyclase and guanylate cyclase and relaxes rat thoracic aorta by releasing nitric oxide

“…If this were the case, then the greater amount of endothelium would generate more NO and the increase in cyclic GMP production in the vascular smooth muscle would be easier to measure. This may be the explanation for the increase in the cyclic nucleotide detected here but not in the earlier experiments (Grace et al, 1987).…”

“…In view of the reported differences in second messenger accumulation for acetylcholine and CGRP, these being cyclic GMP (Griffith et al, 1985) and cyclic AMP (Kubota et al, 1985;Grace et al, 1987) respectively, it appeared possible that another factor and not nitric oxide was being released by CGRP. We recently demonstrated that the relaxations induced by both acetylcholine and human a-CGRP could be inhibited by N0-monomethyl-L-arginine (L-NMMA) and L-NOARG (Gray & Marshall, 1992a), which are reported to inhibit the synthesis of nitric oxide from the terminal guanidino nitrogen of L-arginine (Rees et al, 1989;Moore et al, 1990).…”

“…Open columns represent basal levels of cyclic nucleotides and solid columns represent the levels of cyclic nucleotides after 30 s exposure to human a-CGRP (3 x 10-7 M). Levels of cyclic GMP (a) and cyclic AMP (b) (Brain et al, 1985;Grace et al, 1987).…”

Relaxant Response of Isolated Basilar Arteries to Calcitonin Gene-Related Peptide in Stroke-Prone Spontaneously Hypertensive Rats.

“…It has been demonstrated that CGRP stimulates in tracellular cyclic AMP production by aortic smooth muscle cells (22,24), cerebral arteries (13) and arter ioles (25), and coronary arteries (16), but has no effect on cyclic GMP production (16,(22)(23)(24). These findings suggest that cyclic AMP production by vascular smooth muscle contributes to the relaxation response to CGRP.…”

Vasorelaxation in isolated bone arteries: Vasoactive intestinal peptide, substance P, calcitonin gene-related peptide bradykinin studied in pigs

“…This indicates that the response to CGRP is mediated mainly by a direct effect on the vascular smooth muscle. Reports on CGRP show both an endothelium-dependent pathway (Brain et al 1985, Grace et al 1987 and an endothelium-independent pathway (Edvinsson et al 1985, Brizzolara and Burnstock 1991, Prieto et al 1991, Samuelson and Jernbeck 1991. This may imply variations between different vascular beds and species.…”