title: Vasorelaxation to capsaicin and its effects on calcium influx in  arteries.
abstract: Capsaicin, an activator of the transient potential vanilloid receptor type 1 (TRPV1), is a commonly used pharmacological tool for desensitising sensory nerves. Capsaicin can induce vasorelaxation of isolated blood vessels by activating perivascular TRPV1 receptors, causing the release of vasoactive neuropeptides. This study attempted to characterise the vascular effects of capsaicin in the rat isolated aorta and porcine coronary arteries. Capsaicin elicited concentration-dependent vasorelaxation of both rat aortae and porcine coronary arteries. Capsaicin-induced vasorelaxation of rat aorta was unaffected by a chronic pre-treatment of vessels with capsaicin. Moreover, relaxation was insensitive to the presence of capsazepine, a competitive TRPV1 antagonist, in both the rat aorta and porcine coronary artery. It was hypothesised that capsaicin may be inhibiting calcium influx into smooth muscle cells. Indeed, in vessels incubated in a Ca²⁺-free high-k⁺ buffer, the presence of 30 μM capsaicin significantly inhibited the contractile response to the re-introduction of Ca²⁺. In porcine coronary arteries 100 μM capsaicin completely abolished the contractile response to the re-introduction of Ca²⁺. In addition, capsaicin also abolished the concentration-dependent contraction of porcine coronary arteries induced by the L-type calcium activator Bay-K 8644. Therefore, we suggest that capsaicin causes vascular responses in arteries through the inhibition of L-type Ca²⁺ channels. In summary,we have identified a potential mechanism underlying TRPV1-independent capsaicin-induced vasorelaxation. Our results also question the use of chronic capsaicin pre-treatment in experimental pharmacology in order to elucidate the role of sensory nerves in vascular responses.
authors.affiliation: Cardiovascular Research Group, School of Biomedical Sciences, University of Nottingham Medical School, Queen's Medical Centre, Nottingham, NG7 2UH, United Kingdom.
authors.forename: Jamie J
authors.initials: JJ
authors.lastname: Hopps
authors.forename: William R
authors.initials: WR
authors.lastname: Dunn
authors.forename: Michael D
authors.initials: MD
authors.lastname: Randall
mesh_terms: D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D001012:Aorta, Abdominal / Q000187:drug effects / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000187:drug effects* / Q000378:metabolism; D002211:Capsaicin / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology*; D003331:Coronary Vessels / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013552:Swine; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; C071423:capsazepine; D002211:Capsaicin; D002118:Calcium