Involvement of capsaicin-sensitive neurones in the haemodynamic effects of exogenous vasoactive peptides: studies in conscious, adult Long Evans rats treated neonatally with capsaicin.
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-1, 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, since responses to such peptides (e.g. substance P and calcitonin gene-related peptide) are relatively normal in capsaicin-treated rats.
Bachelard
H
H
Department of Physiology & Pharmacology, Medical School, Queen's Medical Centre, Nottingham.
Gardiner
S M
SM
Kemp
P A
PA
Bennett
T
T
D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology; D001920:Bradykinin / Q000494:pharmacology; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D002211:Capsaicin / Q000494:pharmacology*; D002766:Cholecystokinin / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects*; D009479:Neuropeptides / Q000494:pharmacology*; D051381:Rats; D013373:Substance P / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
D009479:Neuropeptides; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D013373:Substance P; D002766:Cholecystokinin; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin; D001920:Bradykinin