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)