Effects of Nifedipine on Renal and Cardiovascular Responses to Neuropeptide Y in Anesthetized Rats

Abstract

Neuropeptide Y (NPY) acts via multiple receptor subtypes termed Y ₁, Y ₂ and Y ₅. While Y ₁ receptor-mediated effects, e.g., in the vasculature, are often sensitive to inhibitors of L-type Ca ²⁺ channels such as nifedipine, little is known about the role of such channels in Y ₅-mediated effects such as diuresis and natriuresis. Therefore, we explored whether nifedipine affects NPY-induced diuresis and natriuresis. After pre-treatment with nifedipine or vehicle, anesthetized rats received infusions or bolus injections of NPY. Infusion NPY (1 µg/kg/min) increased diuresis and natriuresis, and this was attenuated by intraperitoneal injection of nifedipine (3 µg/kg). Concomitant decreases in heart rate and reductions of renal blood flow were not attenuated by nifedipine. Bolus injections of NPY (0.3, 1, 3, 10 and 30 μg/kg) dose-dependently increased mean arterial pressure and renovascular vascular resistance; only the higher dose of nifedipine (100 μg/kg/min i.v.) moderately inhibited these effects. We conclude that Y ₅-mediated diuresis and natriuresis are more sensitive to inhibition by nifedipine than Y ₁-mediated renovascular effects. Whether this reflects a general sensitivity of Y ₅ receptor-mediated responses or is specific for diuresis and natriuresis remains to be investigated.