HETEROGENEOUS INVOLVEMENT OF ENDOTHELIUM IN CALCITONIN GENE-RELATED PEPTIDE-INDUCED RELAXATION IN CORONARY-ARTERIES FROM RAT

1 The effects of rat- and human-CGRP and capsaicin were studied in isolated rings of rat proximal epicardial (PC) and distal intramyocardial (DC) coronary arteries. 2 The relaxing effect of rat-CGRP was dependent on the level of vessel tone induced by prostaglandin F2-alpha (PGF2-alpha) in PC but not in DC arteries. Submaximally contracted DC and PC arteries were more sensitive to rat- than human-CGRP. There was no difference in sensitivity to rat- and human-CGRP between PC and DC arteries. 3 Substance P elicited a small relaxation only in 4 of the 6 PC arteries tested. PC and DC arteries were concentration-dependently relaxed by capsaicin. The relaxation was partly inhibited by ruthenium red, thus suggesting that capsaicin causes specific release of CGRP from sensory nerve endings in rat coronary arteries. 4 The relaxant effect of rat-CGRP was antagonized by endothelium removal and indomethacin but not methylene blue in endothelium-intact PC arteries. The relaxation in DC arteries was not affected by any of these treatments, indicating a heterogeneous involvement of the endothelium in CGRP-mediated coronary vasodilatation and the release of a cyclo-oxygenase product in PC arteries in rats. 5 Glibenclamide had no inhibitory effect on the CGRP-induced relaxation of PC and DC arteries, thus excluding the involvement of glibenclamide-sensitive K+-channels in the mechanism of action of CGRP in rat coronary arteries.