Rigel D F, Lathrop D A
Department of Pharmacology and Cell Biophysics, University of Cincinnati College of Medicine, Ohio 45267.
Am J Physiol. 1991 Aug;261(2 Pt 2):H463-8. doi: 10.1152/ajpheart.1991.261.2.H463.
Effects of the cardiac neuropeptide vasoactive intestinal polypeptide (VIP) and isoproterenol (ISO) were compared on sinus nodal, subsidiary atrial, and atrioventricular junctional pacemaker automaticity in pentobarbital sodium-anesthetized dogs (n = 14). Autonomic cardiac nerves were decentralized by bilateral vagotomy and stellectomy. VIP and ISO (30, 100, and 300 pmol/kg iv) were administered during sinus rhythm and either after crushing the sinus node to unmask a latent subsidiary atrial pacemaker (n = 7 dogs) or after injecting pentobarbital sodium into the sinus node artery to elicit an atrioventricular junctional pacemaker (n = 7). Spontaneous sinus nodal, subsidiary atrial, and atrioventricular junctional pacemaker rates (after autonomic nerve decentralization) were 142 +/- 4, 114 +/- 3, and 79 +/- 4 beats/min (means +/- SE), respectively. Both VIP and ISO dose dependently increased the rates of all three pacemaker sites. Combined muscarinic-cholinergic (atropine; 0.11 mg/kg iv) and beta-adrenergic receptor blockade (nadolol; 0.5 mg/kg iv) abolished the stimulatory effects of ISO on subsidiary atrial and atrioventricular junctional pacemakers but did not affect the responses to VIP. We conclude that exogenous VIP enhances the automaticity of sinus nodal, subsidiary atrial, and atrioventricular junctional pacemakers independently of muscarinic-cholinergic and beta-adrenergic receptors. Based on the previous demonstration of VIP-immunoreactive nerves throughout the heart, our findings also suggest that endogenous VIP may be involved in cardiac pacemaker regulation.
在戊巴比妥钠麻醉的犬（n = 14）中，比较了心脏神经肽血管活性肠肽（VIP）和异丙肾上腺素（ISO）对窦房结、心房次级起搏点和房室交界区起搏点自律性的影响。通过双侧迷走神经切断术和星状神经节切除术使自主心脏神经去传入。在窦性心律期间，以及在挤压窦房结以暴露潜在的心房次级起搏点后（n = 7只犬）或向窦房结动脉注射戊巴比妥钠以诱发房室交界区起搏点后（n = 7），静脉注射VIP和ISO（30、100和300 pmol/kg）。自主神经去传入后，窦房结、心房次级起搏点和房室交界区起搏点的自发频率分别为142±4、114±3和79±4次/分钟（平均值±标准误）。VIP和ISO均剂量依赖性地增加了所有三个起搏点的频率。联合使用毒蕈碱 - 胆碱能受体阻滞剂（阿托品；0.11 mg/kg静脉注射）和β - 肾上腺素能受体阻滞剂（纳多洛尔；0.5 mg/kg静脉注射）可消除ISO对心房次级起搏点和房室交界区起搏点的刺激作用，但不影响对VIP的反应。我们得出结论，外源性VIP增强了窦房结、心房次级起搏点和房室交界区起搏点的自律性，且与毒蕈碱 - 胆碱能受体和β - 肾上腺素能受体无关。基于先前在整个心脏中发现的VIP免疫反应性神经，我们的研究结果还表明内源性VIP可能参与心脏起搏点的调节。
