Resiniferatoxin‐, capsaicin‐ and CGRP‐evoked porcine coronary vasodilatation is independent of EDRF mechanisms but antagonized by CGRP(8–37)

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Abstract
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 tonein vitrowas 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.It is concluded that RTX, capsaicin and CGRP share several characteristic features with regard to coronary vasodilatation and the present study provides evidence that cardiac vasodilatation upon activation of C‐fibre afferents by both RTX and capsaicin is mediated by CGRP.

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