Cerebrovascular responses to capsaicin in vitro and in situ

Abstract

1 The cerebrovascular effects of capsaicin have been examined in vitro, in feline isolated cerebral arteries (circular segments, 2-3mm long, 300-400pum extended diameter) and, in situ, in pial arterioles (diameter 40-200jum) on the cortical surface of chloralose-anaesthetized cats.2 In isolated middle cerebral arteries, low concentrations of capsaicin (10 1-10-1OM) effected a concentration-dependent relaxation of vessels precontracted with prostaglandin F2l. This relaxant response was markedly attenuated by repeated administration of capsaicin but was minimally affected by the presence of atropine, propranolol, cimetidine or spantide in the tissue bath. 3 In isolated middle cerebral arteries, higher concentrations of capsaicin effected a marked concentration-dependent contraction. This contraction was not modified by 10-6M phentolamine or 10-6 M ketanserin. A markedly reduced contraction by capsaicin was found upon the removal of calcium ions from the buffer solution. Also the calcium entry blocker nimodipine reversed the capsaicin-induced contraction. 4 Subarachnoid perivascular microapplication of capsaicin around individual pial arterioles in situ elicited a biphasic response (an immediate vasoconstriction followed by a sustained vasodilatation). The maximum vasoconstriction was a 60 + 6% reduction in diameter from base line and the maximum vasodilatation a 38 + 7% increase in diameter. Vasodilatation occurred at lower concentrations of capsaicin (EC50, approximately 5 x 10-8M) than those required for vasoconstriction (EC50 3 x 10-7M).5 Trigeminal ganglionectomy 10-16 days before the microapplication abolished the in situ vasodilator effects of capsaicin (10-6M) applied perivascularly, but was without effect on the vasoconstrictor actions of this agent. 6 Repeated administration of capsaicin (10-6M) around the same arteriole resulted in a progressive attenuation of the vasodilator phase of the response, with no modification of the vasoconstrictor phase. 7 The present study suggests that capsaicin-induced cerebral vasodilatation is due to the release of vasoactive agents from cerebrovascular trigeminal nerve fibres, whereas the vasoconstrictor effect 6f capsaicin is due to a direct effect on the cerebral vasculature which is mediated via the transmembrane passage of extracellular calcium.

Structure‐activity relationships of vanilloid receptor agonists for arteriolar TRPV1

“…Another reason was that stimulation of sensory neuronal TRPV1 in the perivascular nerves evokes vasodilatation (Zygmunt et al, 1999), probably obscuring the vasoconstrictor response in many cases. In accordance with this latter mechanism, earlier reports showed concentration-dependent biphasic effects of TRPV1 stimulation; low dose capsaicin evoked dilatation, while higher concentrations resulted in constriction (Edvinsson et al, 1990;Dux et al, 2003). This suggested the involvement of different receptors or different pharmacology for TRPV1-mediating vascular dilatation and constriction.…”

“…Vasoconstriction in response to TRPV1 stimulation was reported decades ago (Molnar and Gyorgy, 1967;Toda et al, 1972;Donnerer and Lembeck, 1982;Duckles, 1986;Edvinsson et al, 1990) and this effect was confirmed later (Szolcsanyi et al, 2001;Dux et al, 2003;Scotland et al, 2004;Keeble and Brain, 2006;Lizanecz et al, 2006). Nonetheless, these responses were not thought to be of interest.…”

Capsaicin-induced Relaxation in Rabbit Coronary Artery.

“…Therefore, it seems likely that activation of cardiac C fiber by capsaicin may relax coronary artery by releasing CGRP. In our present studies, pretreatment with a high concentration of capsaicin, which causes a chemical desensitization of sensory nerves and renders them insensitive to further exposure to capsaicin [4,24], did not change the relaxation responses to subsequently applied capsaicin. Furthermore, pretreatment with capsazepine or ruthenium red, both of which block the release of neuropeptides from sensory nerve [14,22], did not alter the relaxation response to capsaicin.…”

“…In addition to this neuropeptide-mediated effect, capsaicin has a diverse effect on smooth muscle contractility and ion channel activity, depending on the species and preparations. Capsaicin relaxes bronchial smooth muscle through activation of Ca 2+ -activated K + channels [5,24], or constricts cerebral arteries by increasing Ca 2+ influx [4]. The inhibitory effect of capsaicin on Ca 2+ and K + current in cultured aortic smooth muscle cells has also been reported [15].…”

CGRP Receptor Antagonism and Migraine

“…CGRP is the strongest vasodilator found to date, acting via a nonendothelial mechanism and using adenylate cyclase as second messenger. 23,38 Electrical field stimulation or capsaicin treatment 39,40 causes local vasodilatation and release of CGRP from the perivascular nerve fiber endings. These effects are attenuated by administration of a CGRP blocker acting postsynaptically 4 -6,41,42 or a triptan acting at presynaptic sites.…”