Feliciano L, Henning R J
University of South Florida College of Medicine, Department of Medicine, Tampa, USA.
Cardiovasc Res. 1998 Oct;40(1):45-55. doi: 10.1016/s0008-6363(98)00122-9.
To determine the effects of vasoactive intestinal peptide (VIP), released endogenously from cardiac vagal nerves, on coronary artery blood flow (CBF).
We determined the effects of vagal nerve stimulation (VNS) at frequencies of 10, 15, 20, and 30 Hz on left circumflex coronary artery (LCx) blood flow. The increases in CBF during VNS were compared with the increases in CBF produced by exogenous VIP and also nitroglycerin (NTG). In 18 anesthetized open chest mongrel dogs, we blocked the muscarinic and beta-adrenergic receptors with atropine and propranolol. We controlled heart rate and aortic pressure by right atrial pacing and an arterial reservoir. CBF was measured in the LCx with a Doppler flow probe. A 25 gauge catheter was placed in the proximal LCx to inject the VIP receptor antagonist [4Cl-D-Phe6Leu17]VIP, VIP, NTG, or vehicle. CBF, aortic and ventricular pressures, ventricular contractility (+dp/dt(max)) and relaxation (-dp/dt(min)) and the EKG were measured.
VNS (0.5 ms, 20 V, 5 min.) at 20 Hz maximally increased CBF by 62 +/- 14% at 5 min from 71 +/- 10 to 115 +/- 19 ml/min (p < 0.01). VNS at 10, 15, and 30 Hz increased CBF by 6 +/- 1%, 24 +/- 5%, and 24 +/- 7%, respectively (all p < 0.05 vs control). Following 20 Hz VNS, CBF returned toward the baseline over 30 min. Aortic and left ventricular (LV) pressures, LV +dp/dt(max) and LV-dp/dt(min) did not significantly change. After the direct administration of [4Cl-D-Phe6Leu17]VIP into the LCx, VNS increased CBF by only 10 +/- 4% (p = NS). Exogenous VIP, in doses of 9.0 x 10(-11) to 2.1 x 10(-9) mol, increased CBF by 106 +/- 17% to 169 +/- 17% (all p < 0.01 vs control). NTG, in doses of 2.2 x 10(-8) to 1.7 x 10(-7) mol, increased CBF by 101 +/- 15% to 169 +/- 20% (all p < 0.01 vs control). These increases in CBF persisted during the 1 to 2 min injection period and returned to the baseline within 5 min. Neither VIP nor NTG significantly changed the heart rate, aortic or LV pressures, LV +dp/dt(max) or LV -dp/dt(min). VNS at 20 Hz, exogenous VIP, 9.0 x 10(-11) mol, and exogenous NTG, 2.2 x 10(-8) to 4.4 x 10(-8) mol, produced equivalent increases in CBF by analysis of variance determination.
The present experiments suggest that VNS releases VIP which directly dilates coronary arteries and significantly increases coronary artery blood flow.
确定心脏迷走神经内源性释放的血管活性肠肽（VIP）对冠状动脉血流（CBF）的影响。
我们测定了频率为10、15、20和30Hz的迷走神经刺激（VNS）对左旋冠状动脉（LCx）血流的影响。将VNS期间CBF的增加与外源性VIP以及硝酸甘油（NTG）所产生的CBF增加进行比较。在18只麻醉开胸杂种犬中，我们用阿托品和普萘洛尔阻断毒蕈碱和β肾上腺素能受体。通过右心房起搏和动脉储液器控制心率和主动脉压。用多普勒血流探头测量LCx中的CBF。将一根25号导管置于LCx近端以注射VIP受体拮抗剂[4Cl-D-Phe6Leu-17]VIP、VIP、NTG或赋形剂。测量CBF、主动脉和心室压力、心室收缩力（+dp/dt(max)）和舒张（-dp/dt(min)）以及心电图。
20Hz的VNS（0.5ms，20V，5分钟）在5分钟时使CBF最大增加62±14%，从71±10ml/min增加到115±19ml/min（p<0.01）。10、15和30Hz的VNS分别使CBF增加6±1%、24±5%和24±7%（与对照组相比，均p<0.05）。20Hz VNS后，CBF在30分钟内恢复至基线。主动脉和左心室（LV）压力、LV +dp/dt(max)和LV -dp/dt(min)无显著变化。将[4Cl-D-Phe6Leu-17]VIP直接注入LCx后，VNS仅使CBF增加10±4%（p=无统计学意义）。剂量为9.0×10(-11)至2.1×10(-9)mol的外源性VIP使CBF增加106±17%至169±17%（与对照组相比，均p<0.01）。剂量为2.2×10(-8)至1.7×10(-7)mol的NTG使CBF增加101±15%至169±20%（与对照组相比，均p<0.01）。这些CBF的增加在1至2分钟的注射期内持续存在，并在5分钟内恢复至基线。VIP和NTG均未显著改变心率、主动脉或LV压力、LV +dp/dt(max)或LV -dp/dt(min)。通过方差分析确定，20Hz的VNS、剂量为9.0×10(-11)mol的外源性VIP以及剂量为2.2×10(-8)至4.4×10(-8)mol的外源性NTG使CBF产生同等程度的增加。
本实验表明，VNS释放VIP，其直接扩张冠状动脉并显著增加冠状动脉血流。
