Resiniferatoxin-, capsaicin- and CGRP-evoked porcine coronary vasodilatation is independent of EDRF mechanisms but antagonized by CGRP(8-37).
In the present study the effects of activation of capsaicin-sensitive C-fibre afferents by resiniferatoxin and capsaicin as well as the effects of the co-stored peptides calcitonin gene-related peptide substance P and neurokinin A on porcine coronary vascular tone in vitro was investigated. Resiniferatoxin, capsaicin, calcitonin gene-related peptide and neurokinin A all evoked a sustained, concentration-dependent vasodilatation of potassium (60 mM)-precontracted arteries. Substance P also caused vasodilatation of the precontracted arteries but this effect was transient and tachyphylaxis developed rapidly upon repeated administration. Incubation with the calcitonin gene-related peptide fragment (8-37) did not influence the vascular tone per se but markedly attenuated the dilatory effect of calcitonin gene-related peptide and totally abolished the vasodilatation induced by resiniferatoxin and capsaicin while leaving the effect of neurokinin A and substance P unaltered. Incubation with methylene blue, an inhibitor of endothelium-derived relaxing factor mechanisms, which completely blocked the substance P-evoked vasodilatation, as well as substance P-tachyphylaxis, did not influence the vasodilator response to resiniferatoxin, capsaicin or calcitonin gene-related peptide. The neurokinin A-evoked vasodilatation was most likely mediated through activation of neurokinin 1-receptors since it remained unchanged in the presence of the neurokinin 2-receptor antagonist dactinomycin and (Nle10)-neurokinin A (4-10), which selectively activates neurokinin 2-receptors, had only a minor dilatory effect on the precontracted arteries.(ABSTRACT TRUNCATED AT 250 WORDS)
Franco-Cereceda
A
A
Department of Pharmacology, Karolinska Institutet, Stockholm, Sweden.
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology*; D002211:Capsaicin / Q000494:pharmacology*; D003331:Coronary Vessels / Q000187:drug effects / Q000502:physiology*; D003609:Dactinomycin / Q000494:pharmacology; D004224:Diterpenes / Q000494:pharmacology*; D008751:Methylene Blue / Q000494:pharmacology; D015288:Neurokinin A / Q000494:pharmacology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology*; D010446:Peptide Fragments / Q000494:pharmacology*; D013373:Substance P / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology
D004224:Diterpenes; D010446:Peptide Fragments; C058636:calcitonin gene-related peptide (8-37); D003609:Dactinomycin; D009569:Nitric Oxide; D013373:Substance P; D015288:Neurokinin A; C024353:resiniferatoxin; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin; D008751:Methylene Blue