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.