Hashim M A, Harrington W W, Daniels A J, Tadepalli A S
Department of Molecular Pharmacology, Glaxo Wellcome Inc., Research Triangle Park, NC 27709, USA.
Peptides. 1997;18(2):235-9. doi: 10.1016/s0196-9781(96)00295-1.
The hemodynamic effects of neuropeptide Y (NPY) were examined over a dose range of 0.03-30 nmol/kg, i.v., in anesthetized open-chest, ventilated dogs with and without ganglionic blockade. In normal (non-ganglion-blocked) animals, NPY produced significant, dose-dependent, and sustained (lasting 15-45 min) increases in mean arterial blood pressure and systemic vascular resistance (SVR) with a threshold dose of 0.3 nmol/kg and a maximum effective dose of 10 nmol/kg. Cardiac index (CI) decreased at doses > 1 nmol/kg, but stroke volume was not altered; heart rate (HR) decreased significantly at and above the 3 nmol/kg dose. No significant changes were observed in the left ventricular dP/dt (LVdP/dt) or the contractility index (LVdP/dt divided by systolic pressure). In ganglion-blocked animals, pressor and SVR responses to NPY were similar to those seen in normal animals but HR was not affected and a small but significant decrease in CI was seen only at the 30 nmol/kg. Furthermore, whereas LVdP/dt of ganglion-blocked dogs increased significantly at and above the 1 nmol/kg dose, the contractility index increased slightly only with the 10 and 30 nmol/kg doses. These data indicate that NPY produces sustained hypertension in dogs secondary to peripheral vasoconstriction, has a weak, direct positive inotropic action on the heart, and lacks chronotropic effects.
在麻醉开胸、通气的犬类中,静脉注射剂量范围为0.03 - 30 nmol/kg的神经肽Y(NPY),研究其血流动力学效应,实验犬分为有和没有神经节阻断两组。在正常(未阻断神经节)动物中,NPY可使平均动脉血压和全身血管阻力(SVR)显著、剂量依赖性且持续(持续15 - 45分钟)升高,阈剂量为0.3 nmol/kg,最大有效剂量为10 nmol/kg。剂量>1 nmol/kg时心脏指数(CI)降低,但每搏输出量未改变;剂量达到及高于3 nmol/kg时心率(HR)显著降低。左心室dp/dt(LVdP/dt)或收缩性指数(LVdP/dt除以收缩压)未观察到显著变化。在神经节阻断的动物中,NPY引起的升压和SVR反应与正常动物相似,但HR未受影响,仅在30 nmol/kg剂量时CI有小幅但显著的降低。此外,神经节阻断犬的LVdP/dt在剂量达到及高于1 nmol/kg时显著升高,而收缩性指数仅在10和30 nmol/kg剂量时略有升高。这些数据表明,NPY通过外周血管收缩导致犬类持续性高血压,对心脏有微弱的直接正性肌力作用,且无变时作用。