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
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.