INVOLVEMENT OF BETA-2-ADRENOCEPTORS IN THE REGIONAL HEMODYNAMIC-RESPONSES TO BRADYKININ IN CONSCIOUS RATS

Citation
Sm. Gardiner et al., INVOLVEMENT OF BETA-2-ADRENOCEPTORS IN THE REGIONAL HEMODYNAMIC-RESPONSES TO BRADYKININ IN CONSCIOUS RATS, British Journal of Pharmacology, 105(4), 1992, pp. 839-848
Citations number
27
Language
INGLESE
art.tipo
Article
ISSN journal
0007-1188
Volume
105
Issue
4
Year of publication
1992
Pages
839 - 848
Database
ISI
SICI code
0007-1188(1992)105:4<839:IOBITR>2.0.ZU;2-F
Abstract
1 Bradykinin can release neuronal calcitonin gene-related peptide (CGR P) and adrenal medullary catecholamines, both of which could contribut e to its cardiovascular effects in vivo. Therefore, in the main experi ment, regional haemodynamic responses to bolus injections of bradykini n (3 nmol kg-1, i.v.) were assessed in the same chronically-instrument ed, conscious, Long Evans rats in the absence and in the presence of h uman alpha-CGRP [8-37] or ICI 118551, antagonists of CGRP1-receptors a nd beta(2)-adrenoceptors, respectively. The selected doses of these an tagonists caused specific inhibition of responses mediated by exogenou s human alpha-CGRP and beta(2)-adrenoceptor agonists, respectively. 2 Bradykinin administered alone as an i.v. bolus had a slight pressor ef fect accompanied by a marked tachycardia. There were early (at about 3 0 s) increases in flow and conductance in the mesenteric vascular bed, and delayed (at about 90 s), but qualitatively similar, changes in th e hindquarters vascular bed. There were only slight increases in flow and conductance in the renal vascular bed. 3 Human alpha-CGRP [8-37] h ad no statistically significant effects on the responses to bolus dose s of bradykinin. However, in the presence of ICI 118551, the pressor e ffect of bradykinin was significantly enhanced while its tachycardic e ffect was significantly suppressed. The hindquarters vasodilator effec t of bradykinin was converted to a vasoconstriction and there was a sl ight renal vasoconstriction, but the mesenteric vasodilator effect of bradykinin was unchanged by ICI 118551. 4 In subsidiary experiments, i n other animals, it was found that infusion of bradykinin (36 nmol kg- 1 min-1) elicited a pattern of haemodynamic responses similar to that seen with bolus injections and, as in the latter case, the hindquarter s hyperaemic vasodilatation was inhibited by ICI 118551. In the presen ce of mecamylamine (at a dose sufficient to block reflex heart rate re sponses to rises or falls in arterial blood pressure) bolus injection or infusion of bradykinin still elicited increases in renal, mesenteri c and hindquarters blood flow. However, in additional experiments in a drenal demedullated rats (n = 4) the hindquarters hyperaemic effect of bradykinin was absent, although the mesenteric hyperaemic effect rema ined. 5 The results indicate that the increase in hindquarters blood f low following administration of bradykinin in vivo is largely due to a ctivation of beta(2)-adrenoceptors by catecholamines released subseque nt to direct stimulation of the adrenal medulla by the peptide. Howeve r, the bradykinin-induced increase in mesenteric blood flow does not d epend on this mechanism.