Capsaicin-induced vasodilatation of human coronary arteries in vitro is mediated by calcitonin gene-related peptide rather than substance P or neurokinin A.
In the present study the possible influence of capsaicin on human arterial coronary tone in vitro was studied in relation to the vasodilatory properties of calcitonin gene-related peptide (CGRP), substance P (SP) or neurokinin A (NKA). In addition, the influence of vasoactive intestinal polypeptide (VIP) and somatostatin (SOM) on the arteries was investigated. CGRP application to potassium-pre-contracted human epicardial coronary arteries (0.4-0.6 mm in inner diameter) induced a concentration-dependent, long-lasting relaxation. SP also relaxed these pre-contracted arteries, but the relaxation was transient and tachyphylaxis developed rapidly upon repeated administration. SP tachyphylaxis did not influence the relaxatory effects of CGRP. Furthermore, pre-incubation with gossypol, an inhibitor of the formation and release of endothelium-derived relaxing factors (EDRF), completely abolished the effects of SP without influencing the dilatory action of CGRP. NKA only induced a very minor relaxation of the pre-contracted arteries. Both VIP and SOM concentration-dependently relaxed the pre-contracted arteries. Capsaicin evoked a relaxation of the potassium-pre-contracted arteries. This effect was not influenced by SP tachyphylaxis or gossypol incubation. Thus, CGRP but not SP mimics the vasodilatory effects of capsaicin on human coronary arteries. This suggests that CGRP rather than SP is likely to mediate the relaxatory effects seen upon activation of cardiac sensory nerves.
Franco-Cereceda
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Department of Pharmacology, Karolinska Institute, Stockholm, Sweden.
Rudehill
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D000328:Adult; D001158:Arteries / Q000187:drug effects; D001685:Biological Factors / Q000494:pharmacology; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin / Q000494:pharmacology*; D003331:Coronary Vessels / Q000187:drug effects*; D005260:Female; D006801:Humans; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D015288:Neurokinin A / Q000494:pharmacology*; D009479:Neuropeptides / Q000494:pharmacology*; D009569:Nitric Oxide; D013004:Somatostatin / Q000494:pharmacology; D013373:Substance P / Q000494:pharmacology*; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology*
D001685:Biological Factors; D009479:Neuropeptides; D014665:Vasodilator Agents; D009569:Nitric Oxide; D013373:Substance P; D014660:Vasoactive Intestinal Peptide; D013004:Somatostatin; D015288:Neurokinin A; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin