EPICARDIAL BRADYKININ B-2 RECEPTORS ELICIT A SYMPATHOEXCITATORY REFLEX IN RATS

Bradykinin may be generated in the heart during ischemia and is involv ed in nociception. We tested the hypothesis that bradykinin elicits a sympathoexcitatory reflex in rats by stimulating cardiac afferent nerv e fibers. Rats were implanted with femoral catheters for measurement o f blood pressure and heart rate, a bipolar electrode for measurement o f renal sympathetic nerve activity, and a pericardial catheter for int rapericardial injection of substances. Rats were slightly anesthetized with hexobarbital so pain reactions were prevented. Graded doses of b radykinin (2.5, 12, 25 mu g) were injected intravenously or intraperic ardially into control rats, intrapericardially after vagotomy, intrape ricardially after intrapericardial pretreatment with the bradykinin B- 2 receptor antagonist Hoe 140, and intrapericardially after cardiac au tonomic blockade (intrapericardial pretreatment with 10% procaine). Fo r comparison, the serotonin 5-HT3 agonist phenylbiguanide, a substance known to elicit sympathoinhibitory reflexes by cardiac vagal afferent s, and adenosine, putatively inducing sympathoexcitatory responses via the heart, were applied intrapericardially. Bradykinin increased bloo d pressure when administered intrapericardially but decreased blood pr essure when injected intravenously; both intrapericardial and intraven ous bradykinin increased renal sympathetic nerve activity. Intraperica rdial adenosine had no effect on circulatory control. Intrapericardial pretreatment with the B-2 receptor antagonist Hoe 140 completely inhi bited the increases of blood pressure and renal sympathetic nerve acti vity in response to intrapericardial bradykinin but did not affect the responses to intrapericardial phenylbiguanide. Bilateral cervical vag otomy abolished the decreases of blood pressure, heart rate, and renal sympathetic nerve activity after intrapericardial phenylbiguanide but did not influence the responses to intrapericardial bradykinin. Cardi ac autonomic blockade with intrapericardial procaine abolished all res ponses to bradykinin and phenylbiguanide. We conclude that cardiac bra dykinin elicits a sympathoexcitatory reflex by epicardial B-2 receptor s in rats. The afferent portion of the reflex is most likely contained within sympathetic cardiac afferent fibers. Bradykinin may contribute to increased sympathetic nerve activity in pathophysiological situati ons of coronary artery disease and cardiac ischemia.