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Impact of the NO-Sensitive Guanylyl Cyclase 1 and 2 on Renal Blood Flow and Systemic Blood Pressure in Mice

Nitric oxide (NO) modulates renal blood flow (RBF) and kidney function and is involved in blood pressure (BP) regulation predominantly via stimulation of the NO-sensitive guanylyl cyclase (NO-GC), existing in two isoforms, NO-GC1 and NO-GC2. Here, we used isoform-specific knockout (KO) mice and inve...

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Autores principales: Mergia, Evanthia, Thieme, Manuel, Hoch, Henning, Daniil, Georgios, Hering, Lydia, Yakoub, Mina, Scherbaum, Christina Rebecca, Rump, Lars Christian, Koesling, Doris, Stegbauer, Johannes
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5979494/
https://www.ncbi.nlm.nih.gov/pubmed/29570672
http://dx.doi.org/10.3390/ijms19040967
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author Mergia, Evanthia
Thieme, Manuel
Hoch, Henning
Daniil, Georgios
Hering, Lydia
Yakoub, Mina
Scherbaum, Christina Rebecca
Rump, Lars Christian
Koesling, Doris
Stegbauer, Johannes
author_facet Mergia, Evanthia
Thieme, Manuel
Hoch, Henning
Daniil, Georgios
Hering, Lydia
Yakoub, Mina
Scherbaum, Christina Rebecca
Rump, Lars Christian
Koesling, Doris
Stegbauer, Johannes
author_sort Mergia, Evanthia
collection PubMed
description Nitric oxide (NO) modulates renal blood flow (RBF) and kidney function and is involved in blood pressure (BP) regulation predominantly via stimulation of the NO-sensitive guanylyl cyclase (NO-GC), existing in two isoforms, NO-GC1 and NO-GC2. Here, we used isoform-specific knockout (KO) mice and investigated their contribution to renal hemodynamics under normotensive and angiotensin II-induced hypertensive conditions. Stimulation of the NO-GCs by S-nitrosoglutathione (GSNO) reduced BP in normotensive and hypertensive wildtype (WT) and NO-GC2-KO mice more efficiently than in NO-GC1-KO. NO-induced increase of RBF in normotensive mice did not differ between the genotypes, but the respective increase under hypertensive conditions was impaired in NO-GC1-KO. Similarly, inhibition of endogenous NO increased BP and reduced RBF to a lesser extent in NO-GC1-KO than in NO-GC2-KO. These findings indicate NO-GC1 as a target of NO to normalize RBF in hypertension. As these effects were not completely abolished in NO-GC1-KO and renal cyclic guanosine monophosphate (cGMP) levels were decreased in both NO-GC1-KO and NO-GC2-KO, the results suggest an additional contribution of NO-GC2. Hence, NO-GC1 plays a predominant role in the regulation of BP and RBF, especially in hypertension. However, renal NO-GC2 appears to compensate the loss of NO-GC1, and is able to regulate renal hemodynamics under physiological conditions.
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spelling pubmed-59794942018-06-10 Impact of the NO-Sensitive Guanylyl Cyclase 1 and 2 on Renal Blood Flow and Systemic Blood Pressure in Mice Mergia, Evanthia Thieme, Manuel Hoch, Henning Daniil, Georgios Hering, Lydia Yakoub, Mina Scherbaum, Christina Rebecca Rump, Lars Christian Koesling, Doris Stegbauer, Johannes Int J Mol Sci Article Nitric oxide (NO) modulates renal blood flow (RBF) and kidney function and is involved in blood pressure (BP) regulation predominantly via stimulation of the NO-sensitive guanylyl cyclase (NO-GC), existing in two isoforms, NO-GC1 and NO-GC2. Here, we used isoform-specific knockout (KO) mice and investigated their contribution to renal hemodynamics under normotensive and angiotensin II-induced hypertensive conditions. Stimulation of the NO-GCs by S-nitrosoglutathione (GSNO) reduced BP in normotensive and hypertensive wildtype (WT) and NO-GC2-KO mice more efficiently than in NO-GC1-KO. NO-induced increase of RBF in normotensive mice did not differ between the genotypes, but the respective increase under hypertensive conditions was impaired in NO-GC1-KO. Similarly, inhibition of endogenous NO increased BP and reduced RBF to a lesser extent in NO-GC1-KO than in NO-GC2-KO. These findings indicate NO-GC1 as a target of NO to normalize RBF in hypertension. As these effects were not completely abolished in NO-GC1-KO and renal cyclic guanosine monophosphate (cGMP) levels were decreased in both NO-GC1-KO and NO-GC2-KO, the results suggest an additional contribution of NO-GC2. Hence, NO-GC1 plays a predominant role in the regulation of BP and RBF, especially in hypertension. However, renal NO-GC2 appears to compensate the loss of NO-GC1, and is able to regulate renal hemodynamics under physiological conditions. MDPI 2018-03-23 /pmc/articles/PMC5979494/ /pubmed/29570672 http://dx.doi.org/10.3390/ijms19040967 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Mergia, Evanthia
Thieme, Manuel
Hoch, Henning
Daniil, Georgios
Hering, Lydia
Yakoub, Mina
Scherbaum, Christina Rebecca
Rump, Lars Christian
Koesling, Doris
Stegbauer, Johannes
Impact of the NO-Sensitive Guanylyl Cyclase 1 and 2 on Renal Blood Flow and Systemic Blood Pressure in Mice
title Impact of the NO-Sensitive Guanylyl Cyclase 1 and 2 on Renal Blood Flow and Systemic Blood Pressure in Mice
title_full Impact of the NO-Sensitive Guanylyl Cyclase 1 and 2 on Renal Blood Flow and Systemic Blood Pressure in Mice
title_fullStr Impact of the NO-Sensitive Guanylyl Cyclase 1 and 2 on Renal Blood Flow and Systemic Blood Pressure in Mice
title_full_unstemmed Impact of the NO-Sensitive Guanylyl Cyclase 1 and 2 on Renal Blood Flow and Systemic Blood Pressure in Mice
title_short Impact of the NO-Sensitive Guanylyl Cyclase 1 and 2 on Renal Blood Flow and Systemic Blood Pressure in Mice
title_sort impact of the no-sensitive guanylyl cyclase 1 and 2 on renal blood flow and systemic blood pressure in mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5979494/
https://www.ncbi.nlm.nih.gov/pubmed/29570672
http://dx.doi.org/10.3390/ijms19040967
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