Intracerebroventricular administration of NPY increases sympathetic tone selectively in vascular beds

NPY is widely distributed and has broad regulatory actions in the peripheral and central nervous system (CNS) and is especially important in the regulation of cardiovascular responses. CNS administered NPY has been demonstrated to produce both increases and decreases in cardiovascular tone. In this study we evaluated the effect of intracerebroventricular (ICV) administered NPY on cardiovascular tone, regional blood flow dynamics, as well as the mechanism of this action in normal animals. Male rats were instrumented with ICV cannulas and allowed to recover. At the time of the experiment the rats were anesthetized with urethane/chloralose and the femoral artery cannulated for blood pressure determinations. The abdomen was opened and Doppler flow probes were placed around the iliac, renal, and superior mesenteric artery. Mean arterial pressure (MAP), heart rate (HR), iliac, renal, and superior mesenteric flow, as well as the calculated iliac, renal, and superior mesenteric conductance were determined. ICV administered NPY resulted in an increase in MAP and HR, which was associated with decreased flows in the iliac and superior mesenteric vessels while increasing renal flow. Conductance was decreased in the iliac and superior mesenteric vascular beds but not the renal artery. ICV administration of NPY in the presence of a systemically administered alpha1-adrenergic inhibitor, prazosin, attenuated the NPY-mediated effects on MAP as well as vascular conductance in the iliac and superior mesenteric vessels. Additionally, ICV administration of NPY in the presence of a systemically administered beta1-adrenergic inhibition, atenolol, also attenuated the NPY-mediated increase in HR and MAP. Blood flow responses and iliac and superior mesenteric vascular conductance were also attenuated by atenolol pretreatment. In these studies we conclude that lateral ventricular administration of NPY acts to increase systemic MAP and HR and the response is mediated by an increase in sympathetic tone to the heart and especially the splanchnic and skeletal muscle vasculature.