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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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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