Veelken R, Glabasnia A, Stetter A, Hilgers K F, Mann J F, Schmieder R E
Department of Internal Medicine, University of Erlangen-Nürnberg, Germany.
Hypertension. 1996 Oct;28(4):615-21. doi: 10.1161/01.hyp.28.4.615.
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.
缓激肽可能在心肌缺血时在心脏中生成，并参与痛觉感受。我们验证了以下假说：缓激肽通过刺激心脏传入神经纤维在大鼠中引发交感兴奋反射。给大鼠植入股动脉导管用于测量血压和心率，植入双极电极用于测量肾交感神经活动，并植入心包导管用于心包内注射物质。用己巴比妥使大鼠轻度麻醉以防止疼痛反应。将不同剂量的缓激肽（2.5、12、25微克）静脉内或心包内注射到对照大鼠体内，在迷走神经切断术后心包内注射，在心包内预先用缓激肽B2受体拮抗剂Hoe 140预处理后心包内注射，以及在心脏自主神经阻滞（心包内预先用10%普鲁卡因处理）后心包内注射。为作比较，将5-羟色胺5-HT3激动剂苯乙双胍（一种已知通过心脏迷走传入神经引发交感抑制反射的物质）和腺苷（推测通过心脏诱导交感兴奋反应）心包内给药。心包内注射缓激肽时血压升高，但静脉注射时血压降低；心包内和静脉内注射缓激肽均增加肾交感神经活动。心包内注射腺苷对循环控制无影响。用B2受体拮抗剂Hoe 140进行心包内预处理可完全抑制心包内注射缓激肽后血压和肾交感神经活动的升高，但不影响对心包内注射苯乙双胍的反应。双侧颈迷走神经切断术消除了心包内注射苯乙双胍后血压、心率和肾交感神经活动的降低，但不影响对心包内注射缓激肽的反应。心包内注射普鲁卡因进行心脏自主神经阻滞消除了对缓激肽和苯乙双胍的所有反应。我们得出结论，心脏缓激肽通过大鼠的心外膜B2受体引发交感兴奋反射。该反射的传入部分很可能包含在心脏交感传入纤维内。缓激肽可能在冠状动脉疾病和心肌缺血的病理生理情况下导致交感神经活动增加。
