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

Angela Bischoff,Martin C Michel,Martina Stickan-Verfürth

doi:10.3390/molecules26154460

Angela Bischoff, Martin C Michel + Show 1 more

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https://doi.org/10.3390/molecules26154460

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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.

Highlights

Neuropeptide Y (NPY) is a co-transmitter of sympathetic neurons and adrenomedullary cells and contributes to the regulation of cardiovascular [1,2] and renal function [3]
The Y5 receptor has largely been studied in the brain where it is involved in the regulation of food intake [20], but it contributes to the regulation of renal function and glucose metabolism [21]
Infusion of NPY caused minor if any changes of mean arterial pressure (MAP) but rapidly reduced heart rate (HR) by about 30 bpm and renal blood flow (RBF) by about 3 mL/min with corresponding increases in renovascular resistance (RVR)

Summary

Introduction

Neuropeptide Y (NPY) is a co-transmitter of sympathetic neurons and adrenomedullary cells and contributes to the regulation of cardiovascular [1,2] and renal function [3]. Typical effects mediated by Y1 receptors include vasoconstriction in several vascular beds [2] including the mesenteric [5,6,7], renal [8,9,10,11], pulmonary [12]. Y2 receptors have primarily been studied as prejunctional inhibitors of neurotransmitter release, both on sympathetic [16,17] and parasympathetic nerves [18] and in the brain [19]. The Y5 receptor has largely been studied in the brain where it is involved in the regulation of food intake [20], but it contributes to the regulation of renal function and glucose metabolism [21]

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