Dual effects of capsaicin on responses of the rabbit ear artery to field stimulation

Abstract

1 The effects of capsaicin (Cap) on contractions of ring segments of rabbit ear artery induced by field stimulation were studied.2 At low concentrations (0.3-3 gM) Cap caused transient enhancement and at higher concentrations (above 3 pM) inhibition of stimulation-induced contractions, without affecting noradrenaline (NA)-induced contractions. 3 In the continuous presence of high concentrations of Cap, rebound facilitation was observed after inhibition, and at this stage, Cap elicited less inhibition of the response. 4 Repeated application of Cap at 60 min intervals irreversibly desensitized the artery to the inhibitory effect of Cap. 5 Functional removal of the endothelium enhanced the facilitatory effect of low concentrations of Cap and attenuated its inhibitory effect. 6 Pretreatment with indomethacin abolished the facilitatory effect of Cap and enhanced its inhibitory effect, indicating that prostaglandins are involved in the action of Cap. The effect of indomethacin was more marked in preparations from which the endothelium had been removed. 7 Desensitization to substance P (SP) or substance K (SK), did not affect either the inhibitory or the facilitatory effect of Cap. 8 These results suggest that the dual effects of Cap on stimulation-induced contractions of rabbit ear artery may arise from the release of multiple mediators that act prejunctionally to modulate NA release. The stimulant effect seems to be mediated by prostanoids, while the inhibitory effect seems to be caused by a substance(s) that is not SP or SK. The possibility that the mediator is calcitonin gene-related peptide requires further study.

Electrophysiological effects of activating the peptidergic primary afferent innervation of rat mesenteric arteries

“…amplitude indicates that this agent enhances purinergic neuromuscular transmission. There are previous reports that capsaicin increases sympathetic nerve‐evoked contractions of mouse and rat vas deferens and rabbit ear artery ( Moritoki et al , 1987 ; 1990; Parlani et al , 1995 ). In mouse vas deferens, in the presence of CGRP 8–37 , capsaicin produced a transient increase in the motor response evoked by sympathetic nerve stimulation that is blocked by the tachykinin receptor antagonist, CP96,347 ( Parlani et al , 1995 ).…”

“…In contrast, the facilitatory effect of capsaicin in both rat vas deferens ( Moritoki et al , 1987 ) and rabbit ear artery ( Moritoki et al , 1990 ) does not desensitize, questioning whether its actions in these tissues are mediated through the excitation of the primary afferent axons. In rabbit ear artery, low concentrations of capsaicin increased sympathetic nerve‐evoked contractions, whereas higher concentrations were inhibitory.…”

“…In this tissue, the inhibitory action of capsaicin did desensitize, suggesting that this effect is mediated through the activation of primary afferent axons. The cyclooxygenase inhibitor, indomethacin, blocked the facilitatory effect of capsaicin in rabbit ear artery, indicating that prostaglandins are involved ( Moritoki et al , 1990 ). In mouse and rat vas deferens and rabbit ear artery, as capsaicin did not increase contractions to exogenous application of the neurotransmitters, the facilitatory effects of this agent on nerve‐evoked contraction are suggested to be mediated through an increase in neurotransmitter release from the sympathetic nerve endings ( Moritoki et al , 1987 ; 1990; Parlani et al , 1995 ).…”

Stimulation by Capsaicin of Gastric Alkaline Secretion in Anesthetized Rats

“…Other studies also showed involvement of PGs in the cytoprotective action of capsaicin against ethanol (9,10) or in the capsaicin-induced gastric hyperemic re sponse (11). However, the relation of capsaicin to PG generation is not without controversy; capsaicin may enhance the formation of PGs in vascular tissues of rab bits (19), while no effect on PG generation is observed in the rat gastric mucosa and other tissues (2,20). In domethacin has several other effects that are unrelated to PGs (21,22), and these actions might be associated with suppression of the HC03 response to capsaicin.…”

Peptidergic sensory neurons in the control of vascular functions: Mechanisms and significance in the cutaneous and splanchnic vascular beds

“…However, its specificity for afferent neurons is not absolute, and some of the acute effects of the drug on blood vessels appear to result from a direct action on vascular muscle (Donnerer and Lembeck 1982;Duckles 1986;B6ny et al 1989;Edvinsson et al 1990; Moritoki et al 1990) and endothelium (Kenins et al 1984). The label "capsaicin sensitive" is applied to those afferent neurons which acutely are excited and in the long term are damaged by the drug.…”