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

Abstract

Neuropeptide Y (NPY) acts via multiple receptor subtypes termed Y1, Y2 and Y5. While Y1 receptor-mediated effects, e.g., in the vasculature, are often sensitive to inhibitors of L-type Ca2+ channels such as nifedipine, little is known about the role of such channels in Y5-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 Y5-mediated diuresis and natriuresis are more sensitive to inhibition by nifedipine than Y1-mediated renovascular effects. Whether this reflects a general sensitivity of Y5 receptor-mediated responses or is specific for diuresis and natriuresis remains to be investigated.

Gβγ subunit signalling underlies neuropeptide Y‐stimulated vasoconstriction in rat mesenteric and coronary arteries

“…Since its discovery in the late 1980s, the vasoactive properties of NPY have been widely studied. When infused in vivo, NPY increases blood pressure and decreases regional blood flow (Bischoff et al, 2021 ; Malmstrom et al, 1997 ). In ex vivo studies with isolated arteries, NPY is a vasoconstrictor in a variety of species across different vascular beds (Nilsson et al, 1996 ; Prieto et al, 2000 ; Xia et al, 1992 ), including coronary arteries of rat and human (Herring et al, 2019 ; Prieto et al, 1998 ; Tseng et al, 1988 ).…”