Hemodynamic profile of neuropeptide Y in dogs: effect of ganglionic blockade.
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.
Hashim
M A
MA
Department of Molecular Pharmacology, Glaxo Wellcome Inc., Research Triangle Park, NC 27709, USA.
Harrington
W W
WW
Daniels
A J
AJ
Tadepalli
A S
AS
D000704:Analysis of Variance; D000818:Animals; D001011:Aorta / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005726:Ganglia, Parasympathetic / Q000502:physiology*; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D008297:Male; D009478:Neuropeptide Y / Q000494:pharmacology*; D012039:Regional Blood Flow / Q000187:drug effects; D013318:Stroke Volume / Q000187:drug effects; D014628:Vagotomy; D014655:Vascular Resistance / Q000187:drug effects
D009478:Neuropeptide Y