Feliciano L, Henning R J
James A. Haley Veterans' Administration Hospital, Division of Cardiology, University of South Florida College of Medicine, Tampa 33612, USA.
J Auton Nerv Syst. 1998 Jan 19;68(1-2):78-88. doi: 10.1016/s0165-1838(97)00109-4.
Vasoactive intestinal peptide (VIP) is present in post-ganglionic vagal nerve fibers in the coronary arteries and right ventricle but no significant amounts are found in the left ventricle. We determined the effects of VIP, released endogenously from cardiac vagal nerves, on the circumflex mean coronary artery pressure and on right and left ventricular (RV and LV) contractility (dP/dtmax) and relaxation (dP/dtmin). In 20 anesthetized, open chest mongrel dogs, the cervical vagus nerves and cardiac sympathetic ansa subclaviae were isolated and transected. Electrodes were applied to the cardiac segments of the right and left vagus nerves for subsequent stimulation. The muscarinic and beta-adrenergic receptors were blocked with atropine and propranolol, respectively. The heart rate was controlled by either producing atrioventricular node block in 10 dogs and pacing the ventricles (series 1) or by right atrial pacing in 10 separate dogs (series 2). Coronary artery blood flow was controlled by perfusing the circumflex coronary artery in each dog with femoral arterial blood at a controlled flow rate. Coronary artery pressure, ventricular and aortic pressures and dP/dt were continuously measured. Experiments were performed prior to and after the administration of [4Cl-D-Phe6,Leu17]VIP, a sensitive and selective VIP antagonist. Vagal nerve stimulation at 20 Hz (0.5 ms, 20 V) for 5 min significantly decreased the circumflex mean coronary artery pressure by 17% from the control value of 95+/-2 mmHg in series 1 and by 13% from the control value of 109+/-2 mmHg in series 2 (both p < 0.005). Aortic, LV and RV systolic and end-diastolic pressures, LV dP/dtmax and dP/dtmin, and the EKG did not change. In contrast, RV dP/dtmax and dP/dtmin increased by 22% (p < 0.04) and 23% (p < 0.02), respectively, in series 1 and by 26% (p < 0.02) and 33% (p < 0.01), respectively, in series 2. The VIP antagonist, [4Cl-D-Phe6,Leu17]VIP, directly injected into the left circumflex coronary artery, had no effect on coronary, aortic or ventricular pressures, ventricular dP/dt or the EKG. However, 20 Hz vagal stimulation in the presence of the VIP antagonist did not decrease circumflex mean coronary artery pressure. In addition, vagal stimulation, in the presence of the VIP antagonist, had no effect on LV pressures or dP/dt but increased RV dP/dtmax and dP/dtmin. RV dP/dtmax increased by 16% (p < 0.01) and RV dP/dtmin increased by 22% (p < 0.04), respectively, in series 1 and by 27 and 24%, respectively, in series 2 (both p < 0.01). Vagal nerve stimulation during muscarinic and beta-adrenergic blockade releases VIP or a 'VIP-like' substance that significantly decreases circumflex coronary artery vascular resistance and increases RV dP/dtmax and dP/dtmin.
血管活性肠肽（VIP）存在于冠状动脉和右心室的节后迷走神经纤维中，但在左心室中未发现大量存在。我们确定了心脏迷走神经内源性释放的VIP对左旋支平均冠状动脉压力以及右心室和左心室（RV和LV）收缩力（dP/dtmax）和舒张（dP/dtmin）的影响。在20只麻醉的、开胸的杂种犬中，分离并切断颈迷走神经和心脏交感锁骨下袢。将电极应用于左右迷走神经的心脏节段以便后续刺激。分别用阿托品和普萘洛尔阻断毒蕈碱能和β-肾上腺素能受体。通过在10只犬中产生房室结阻滞并起搏心室（系列1）或在另外10只犬中进行右心房起搏（系列2）来控制心率。通过以受控流速用股动脉血灌注每只犬的左旋支冠状动脉来控制冠状动脉血流。连续测量冠状动脉压力、心室和主动脉压力以及dP/dt。在给予[4Cl-D-Phe6,Leu17]VIP（一种敏感且选择性的VIP拮抗剂）之前和之后进行实验。在系列1中，以20Hz（0.5ms，20V）刺激迷走神经5分钟，使左旋支平均冠状动脉压力从对照值95±2mmHg显著降低17%，在系列2中从对照值109±2mmHg显著降低13%（两者p<0.005）。主动脉、左心室和右心室的收缩压和舒张压、左心室dP/dtmax和dP/dtmin以及心电图均未改变。相比之下，在系列1中，右心室dP/dtmax和dP/dtmin分别增加22%（p<0.04）和23%（p<0.02），在系列2中分别增加26%（p<0.02）和33%（p<0.01）。直接注入左旋支冠状动脉的VIP拮抗剂[4Cl-D-Phe6,Leu17]VIP对冠状动脉、主动脉或心室压力、心室dP/dt或心电图没有影响。然而，在存在VIP拮抗剂的情况下，20Hz迷走神经刺激并未降低左旋支平均冠状动脉压力。此外，在存在VIP拮抗剂的情况下，迷走神经刺激对左心室压力或dP/dt没有影响，但增加了右心室dP/dtmax和dP/dtmin。在系列1中，右心室dP/dtmax增加16%（p<0.01），右心室dP/dtmin增加22%（p<0.04），在系列2中分别增加27%和24%（两者p<0.01）。在毒蕈碱能和β-肾上腺素能阻断期间，迷走神经刺激释放VIP或一种“类VIP”物质，该物质可显著降低左旋支冠状动脉血管阻力并增加右心室dP/dtmax和dP/dtmin。
