Epicardial Bradykinin B ₂ Receptors Elicit a Sympathoexcitatory Reflex in Rats

Abstract

Bradykinin may be generated in the heart during ischemia and is involved in nociception. We tested the hypothesis that bradykinin elicits a sympathoexcitatory reflex in rats by stimulating cardiac afferent nerve fibers. Rats were implanted with femoral catheters for measurement of blood pressure and heart rate, a bipolar electrode for measurement of renal sympathetic nerve activity, and a pericardial catheter for intrapericardial injection of substances. Rats were slightly anesthetized with hexobarbital so pain reactions were prevented. Graded doses of bradykinin (2.5, 12, 25 micrograms) were injected intravenously or intrapericardially into control rats, intrapericardially after vagotomy, intrapericardially after intrapericardial pretreatment with the bradykinin B2 receptor antagonist Hoe 140, and intrapericardially after cardiac autonomic blockade (intrapericardial pretreatment with 10% procaine). For comparison, the serotonin 5-HT3 agonist phenylbiguanide, a substance known to elicit sympathoinhibitory reflexes by cardiac vagal afferents, and adenosine, putatively inducing sympathoexcitatory responses via the heart, were applied intrapericardially. Bradykinin increased blood pressure when administered intrapericardially but decreased blood pressure when injected intravenously; both intrapericardial and intravenous bradykinin increased renal sympathetic nerve activity. Intrapericardial adenosine had no effect on circulatory control. Intrapericardial pretreatment with the B2 receptor antagonist Hoe 140 completely inhibited the increases of blood pressure and renal sympathetic nerve activity in response to intrapericardial bradykinin but did not affect the responses to intrapericardial phenylbiguanide. Bilateral cervical vagotomy 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. Cardiac autonomic blockade with intrapericardial procaine abolished all responses to bradykinin and phenylbiguanide. We conclude that cardiac bradykinin elicits a sympathoexcitatory reflex by epicardial B2 receptors 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 situations of coronary artery disease and cardiac ischemia.

Afferent fibers involved in the bradykinin-induced cardiovascular reflexes from the ovary in rats

“…This result is in accord with other reports that showed that bilateral vagotomy does not affect cardiovascular responses induced by bradykinin application to the heart (Gorman et al, 1983;Gorman and Zucker, 1984;Niitani et al, 1988;Veelken et al, 1996) or abdominal visceral organ such as the gallbladder (Longhurst and Ordway, 1983). In contrast bradykinin applied to the heart is known to stimulate cardiac vagal afferents (Kaufman et al, 1980;Hisata et al, 2006).…”

Cardiovascular effects of peptide kinin B2 receptor antagonists in rats

“…Indeed, the present and previous studies indicate that exogenously administered BK induced a biphasic effect on HR: an immediate bradycardia was followed by a delayed tachycardia. Although these effects could represent reflex adaptations to the vascular effects, there is evidence that BK-induced bradycardia is due to the triggering of a local (intramural) reflex mechanism (Izrailtyan and Kresh 1997), whereas tachycardia could be attributed to either a BK-activated sympathoexcitatory reflex (Veelken et al 1996) or a local modulatory effect of BK on noradrenaline release from sympathetic nerve terminals (Seyedi et al 1997); in any case, a sympathoexcitatory reflex is also facilitated by the preceding simultaneous bradycardia and hypotension.…”

Responses of thoracic spinal neurons to activation and desensitization of cardiac TRPV1-containing afferents in rats

“…bradykinin; capsaicin; resiniferatoxin; sympathetic afferent; vagal afferent MYOCARDIAL ISCHEMIA RELEASES several metabolites, including bradykinin (BK) and protons, which activate cardiac chemosensitive and mechanoreceptive receptors and elicit angina pectoris and cardiovascular responses (8 -14, 39). Physiological and pharmacological studies show that BK activates cardiac nociceptors and sympathoexcitatory responses via kinin B2 receptors located in thinly myelinated A␦ and unmyelinated C-fiber afferent endings in the heart (1,23,39,40). The afferent fibers transmitting the action potentials enter the upper thoracic spinal cord where spinal neurons, spinothalamic tract cells, spinoreticular tract, and other ascending pathway neurons process this information (2-6, 27).…”