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

Neuropeptide Y (NPY) acts via multiple receptor subtypes termed Y<sub>1</sub>, Y<sub>2</sub> and Y<sub>5</sub>. While Y<sub>1</sub> receptor-mediated effects, e.g., in the vasculature, are often sensitive to inhibitors of L-type Ca<sup>2+</sup...

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Main Authors: Angela Bischoff, Martina Stickan-Verfürth, Martin C. Michel
Format: Article
Language:English
Published: MDPI AG 2021-07-01
Series:Molecules
Subjects:
Online Access:https://www.mdpi.com/1420-3049/26/15/4460
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spelling doaj-0f495b1efc5b4964a24047b2a4d105682021-08-06T15:28:48ZengMDPI AGMolecules1420-30492021-07-01264460446010.3390/molecules26154460Effects of Nifedipine on Renal and Cardiovascular Responses to Neuropeptide Y in Anesthetized RatsAngela Bischoff0Martina Stickan-Verfürth1Martin C. Michel2Arensia Exploratory Medicine GmbH, 20225 Düsseldorf, GermanyDepartment of Nephrology and of Particle Therapy, University Hospital Essen, West German Proton Therapy Centre, 45147 Essen, GermanyDepartment of Pharmacology, Johannes Gutenberg University, 55131 Mainz, GermanyNeuropeptide Y (NPY) acts via multiple receptor subtypes termed Y<sub>1</sub>, Y<sub>2</sub> and Y<sub>5</sub>. While Y<sub>1</sub> receptor-mediated effects, e.g., in the vasculature, are often sensitive to inhibitors of L-type Ca<sup>2+</sup> channels such as nifedipine, little is known about the role of such channels in Y<sub>5</sub>-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<sub>5</sub>-mediated diuresis and natriuresis are more sensitive to inhibition by nifedipine than Y<sub>1</sub>-mediated renovascular effects. Whether this reflects a general sensitivity of Y<sub>5</sub> receptor-mediated responses or is specific for diuresis and natriuresis remains to be investigated.https://www.mdpi.com/1420-3049/26/15/4460neuropeptide YY<sub>1</sub> receptorY<sub>5</sub> receptornifedipineblood pressurerenal blood flow
collection DOAJ
language English
format Article
sources DOAJ
author Angela Bischoff
Martina Stickan-Verfürth
Martin C. Michel
spellingShingle Angela Bischoff
Martina Stickan-Verfürth
Martin C. Michel
Effects of Nifedipine on Renal and Cardiovascular Responses to Neuropeptide Y in Anesthetized Rats
Molecules
neuropeptide Y
Y<sub>1</sub> receptor
Y<sub>5</sub> receptor
nifedipine
blood pressure
renal blood flow
author_facet Angela Bischoff
Martina Stickan-Verfürth
Martin C. Michel
author_sort Angela Bischoff
title Effects of Nifedipine on Renal and Cardiovascular Responses to Neuropeptide Y in Anesthetized Rats
title_short Effects of Nifedipine on Renal and Cardiovascular Responses to Neuropeptide Y in Anesthetized Rats
title_full Effects of Nifedipine on Renal and Cardiovascular Responses to Neuropeptide Y in Anesthetized Rats
title_fullStr Effects of Nifedipine on Renal and Cardiovascular Responses to Neuropeptide Y in Anesthetized Rats
title_full_unstemmed Effects of Nifedipine on Renal and Cardiovascular Responses to Neuropeptide Y in Anesthetized Rats
title_sort effects of nifedipine on renal and cardiovascular responses to neuropeptide y in anesthetized rats
publisher MDPI AG
series Molecules
issn 1420-3049
publishDate 2021-07-01
description Neuropeptide Y (NPY) acts via multiple receptor subtypes termed Y<sub>1</sub>, Y<sub>2</sub> and Y<sub>5</sub>. While Y<sub>1</sub> receptor-mediated effects, e.g., in the vasculature, are often sensitive to inhibitors of L-type Ca<sup>2+</sup> channels such as nifedipine, little is known about the role of such channels in Y<sub>5</sub>-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<sub>5</sub>-mediated diuresis and natriuresis are more sensitive to inhibition by nifedipine than Y<sub>1</sub>-mediated renovascular effects. Whether this reflects a general sensitivity of Y<sub>5</sub> receptor-mediated responses or is specific for diuresis and natriuresis remains to be investigated.
topic neuropeptide Y
Y<sub>1</sub> receptor
Y<sub>5</sub> receptor
nifedipine
blood pressure
renal blood flow
url https://www.mdpi.com/1420-3049/26/15/4460
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