Possible involvement of capsaicin-sensitive sensory nerves in the regulation of intestinal blood flow in the dog

1 Capsaicin (Cap) enhanced the twitch response of the epididymal and prostatic portions of rat vas deferens induced by field stimulation at 0.1 Hz. The effect of Cap was reproducible and showed no desensitization. 2 Prazosin, and pretreatment with reserpine or Cap did not affect the potentiating effect of Cap, whereas pretreatment with 6-hydroxydopamine abolished the action of Cap. 3 Cap tended to attenuate the contractions induced by noradrenaline, tyramine and ATP. 4 Like Cap, substance K and substance P augmented the twitch response without causing desensitization, but their effects differed somewhat from that of Cap. Calcitonin gene-related peptide inhibited the twitch response. 5 These results suggest that Cap enhances a stimulation-induced, prazosin-resistant non-adrenergic twitch response of rat vas deferens through an as yet undefined prejunctional mechanism. This mechanism is possibly mediated by some peptide released in response to Cap from sensory neurones, which in turn acts on sympathetic nerves and increases stimulation-induced release of a mediator or cotransmitter responsible for the non-adrenergic twitch response. However, the possibility that Cap has a direct action on sympathetic nerves cannot be ruled out.

Section: Introductionmentioning

confidence: 85%

Section: Discussionmentioning

confidence: 99%

Capsaicin enhances the non‐adrenergic twitch response of rat vas deferens

Moritoki¹,

Iwamoto²,

Kanaya³

et al. 1987

“…It is now well documented that some unmyelinated primary afferent neurones sensitive to capsaicin contain a variety of peptides, including substance P (SP) and calcitonin generelated peptide (CGRP) (Skofitsch & Jacobowitz, 1985;Buck & Burks, 1986;Franco-Cereceda et al, 1987), which have potent cardiovascular effects (Pernow, 1983;Sigrist et al, 1986;Dipette et al, 1987;Lappe et al, 1987;Gardiner et al, 1988;1989a,b,c). In several animal species, it has been demonstrated that the peripheral endings of capsaicin-sensitive, primary afferents are widely distributed throughout peripheral tissues, usually in association with blood vessels (Furness et al, 1982;Barja et al, 1983;Rozsa et al, 1984;Lundberg et al, 1985;Uddmann et al, 1986;Wharton et al, 1986;Wharton & Gulbenkian, 1987;Martling et al, 1988;Hottenstein et al, 1991). This observation raises the possibility that these neurones may be involved with the regulation of vascular tone.…”

Section: Introductionmentioning

confidence: 99%

Involvement of capsaicin‐sensitive neurones in the haemodynamic effects of exogenous vasoactive peptides: studies in conscious, adult Long Evans rats treated neonatally with capsaicin

Bachelard

Gardiner

Kemp

et al. 1992

1 The regional haemodynamic effects of i.v. bolus injections of bradykinin (0.05 or 0.5 nmol), cholecystokinin (0.175 or 1.75 nmol), substance P (0.01 or 0.1 nmol) and calcitonin gene-related peptide (0.05 or 0.5 nmol) were assessed in conscious, adult Long Evans rats that had been treated neonatally with either capsaicin (50 mg kg'-, s.c.) or vehicle. 2 In vehicle-treated rats, both doses of bradykinin were without effect on blood pressure, but caused tachycardia and hindquarters vasodilatation. Moreover, after the higher dose there were dilatations in the renal and superior mesenteric vascular beds. In capsaicin-treated rats the hindquarters vasodilator effects elicited by both doses of bradykinin were significantly reduced, while the tachycardia and responses in the renal and superior mesenteric vascular beds were unchanged. 3 In vehicle-treated rats, cholecystokinin caused dose-dependent increases in blood pressure accompanied by renal, superior mesenteric and hindquarters vasoconstriction followed, after the higher dose, by a hindquarters vasodilatation. The lower dose produced a tachycardia, while there was a bradycardia followed by a tachycardia after the higher dose. In capsaicin-treated rats, the pressor response, as well as the renal vasoconstrictor effects of cholecystokinin, were greater than in vehicle-treated rats, while the heart rate, superior mesenteric or hindquarters responses were not different. 4 In vehicle-treated rats, substance P produced a dose-dependent depressor response and tachycardia accompanied by dilatations in the renal and hindquarters vascular beds and constriction in the superior mesenteric vascular bed. In capsaicin-treated rats, the responses to the lower dose of substance P were not different from those in vehicle-treated rats, while the depressor response to the higher dose of substance P was slightly less than in vehicle-treated rats and the renal vasodilatation was absent. 5 In vehicle-treated rats, calcitonin gene-related peptide caused dose-dependent hypotensive and tachycardic effects associated with dilatations in renal and hindquarters vascular beds and a constriction in the superior mesenteric vascular bed. After the higher dose, the renal vasodilatation was followed by a modest vasoconstriction. In capsaicin-treated rats, the depressor responses to both doses of calcitonin generelated peptide were slightly more prolonged than in vehicle-treated animals, whereas the heart rate and renal and mesenteric vascular conductance changes were not significantly different. However, there was a more sustained hindquarters vasodilator response to the higher dose of calcitonin gene-related peptide in the capsaicin-treated rats. 6 The results suggest that peripheral, capsaicin-sensitive neurones are involved in the cardiovascular responses to exogenous bradykinin and cholecystokinin in conscious rats. It does not appear that the extent of involvement of these neurones is underestimated on account of development of marked supersensitivity to the peptides they normally release, si...

“…The actions of Cap on blood vessels described so far are postjunctional effects (Rozsa et al, 1984;Duckles, 1986): no prejunctional effects on blood vessels have yet been shown, although a prejunctional effect of Cap, irrespective of its direct or indirect action, is well documented for intestinal smooth muscle (Szolcsanyi & Bartho, 1979;Bartho et al, 1982;Chahl, 1982;Bartho & Vizi, 1985). We have shown that in rat vas deferens, Cap enhanced the stimulation-induced twitch response by a prejunctional mechanism (Moritoki et al, 1987).…”

Section: Introduction Methodsmentioning

confidence: 62%

“…In blood vessels, Cap has been shown to cause either dilatation or contraction, depending on the species and portion of the vessels used (Duckles, 1986). Cap-induced increase in intestinal blood flow is thought to be mediated by SP (Rozsa et al, 1984;. However, in some preparations, such as guinea-pig atria (Lundberg et al, 1984;Zernig et al, 1984) and cat cerebral artery (Duckles, 1986), the role of SP as a mediator of the action of Cap is controversial.…”

Section: Introduction Methodsmentioning

confidence: 99%

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

Moritoki

Takase

Tanioka

1990

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.