Specific receptors for bradykinin-induced cardiac sympathetic chemoreflex in the dog.

Bradykinin (BK, 0.03-1 microgram), capsaicin (1 microgram) or potassium chloride (KCl, 13 mumol) applied to the epicardium of the left ventricle of anaesthetized, open-chest dogs, caused reflex tachycardia and pressor effects, whereas des-Arg9-BK (1-100 micrograms), a selective bradykinin B1-receptor agonist, failed to produce any cardiovascular response. Superfusion of the epicardium with a selective B1-receptor antagonist, des-Arg9-[Leu8]BK (50-100 micrograms/min) had no effect on reflex responses to epicardial BK (0.03-0.1 microgram). However, the selective B2-receptor antagonist, D-Arg-[Hyp3,Thi5,8,D-Phe7]BK (10-25 micrograms/min) abolished the reflex effects of 0.03 and 0.1 microgram BK and reduced by 50 to 70% the responses to 1 microgram BK. Another B2-receptor antagonist [Thi6,9,D-Phe8]kallidin (10-50 micrograms/min) also reduced (30-70%) responses to 1 microgram BK. The antagonism was reversible and specific for BK since reflex responses to epicardial application of either capsaicin or KCl were not affected. The results indicate that BK interacts with B2-receptors, probably located on terminals and/or axons of sympathetic afferents supplying the dog heart, to activate a cardiac sympathetic chemoreflex.