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NOS Inhibition Enhances Myogenic Tone by Increasing Rho-Kinase Mediated Ca(2+) Sensitivity in the Male but Not the Female Gerbil Spiral Modiolar Artery

Cochlear blood flow regulation is important to prevent hearing loss caused by ischemia and oxidative stress. Cochlear blood supply is provided by the spiral modiolar artery (SMA). The myogenic tone of the SMA is enhanced by the nitric oxide synthase (NOS) blocker L-N(G)-Nitro-Arginine (LNNA) in male...

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Detalles Bibliográficos
Autores principales: Reimann, Katrin, Krishnamoorthy, Gayathri, Wangemann, Philine
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3536759/
https://www.ncbi.nlm.nih.gov/pubmed/23301097
http://dx.doi.org/10.1371/journal.pone.0053655
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author Reimann, Katrin
Krishnamoorthy, Gayathri
Wangemann, Philine
author_facet Reimann, Katrin
Krishnamoorthy, Gayathri
Wangemann, Philine
author_sort Reimann, Katrin
collection PubMed
description Cochlear blood flow regulation is important to prevent hearing loss caused by ischemia and oxidative stress. Cochlear blood supply is provided by the spiral modiolar artery (SMA). The myogenic tone of the SMA is enhanced by the nitric oxide synthase (NOS) blocker L-N(G)-Nitro-Arginine (LNNA) in males, but not in females. Here, we investigated whether this gender difference is based on differences in the cytosolic Ca(2+) concentration and/or the Ca(2+) sensitivity of the myofilaments. Vascular diameter, myogenic tone, cytosolic Ca(2+), and Ca(2+) sensitivity were evaluated in pressurized SMA segments isolated from male and female gerbils using laser-scanning microscopy and microfluorometry. The gender difference of the LNNA-induced tone was compared, in the same vessel segments, to tone induced by 150 mM K(+) and endothelin-1, neither of which showed an apparent gender-difference. Interestingly, LNNA-induced tone in male SMAs was observed in protocols that included changes in intramural pressure, but not when the intramural pressure was held constant. LNNA in male SMAs did not increase the global Ca(2+) concentration in smooth muscle cells but increased the Ca(2+) sensitivity. This increase in the Ca(2+) sensitivity was abolished in the presence of the guanylyl cyclase inhibitor ODQ or by extrinsic application of either the nitric oxide (NO)-donor DEA-NONOate or the cGMP analog 8-pCPT-cGMP. The rho-kinase blocker Y27632 decreased the basal Ca(2+) sensitivity and abolished the LNNA-induced increase in Ca(2+) sensitivity in male SMAs. Neither LNNA nor Y27632 changed the Ca(2+) sensitivity in female SMAs. The data suggest that the gender difference in LNNA-induced tone is based on a gender difference in the regulation of rho-kinase mediated Ca(2+) sensitivity. Rho-kinase and NO thus emerge as critical factors in the regulation of cochlear blood flow. The larger role of NO-dependent mechanisms in male SMAs predicts greater restrictions on cochlear blood flow under conditions of impaired endothelial cell function.
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spelling pubmed-35367592013-01-08 NOS Inhibition Enhances Myogenic Tone by Increasing Rho-Kinase Mediated Ca(2+) Sensitivity in the Male but Not the Female Gerbil Spiral Modiolar Artery Reimann, Katrin Krishnamoorthy, Gayathri Wangemann, Philine PLoS One Research Article Cochlear blood flow regulation is important to prevent hearing loss caused by ischemia and oxidative stress. Cochlear blood supply is provided by the spiral modiolar artery (SMA). The myogenic tone of the SMA is enhanced by the nitric oxide synthase (NOS) blocker L-N(G)-Nitro-Arginine (LNNA) in males, but not in females. Here, we investigated whether this gender difference is based on differences in the cytosolic Ca(2+) concentration and/or the Ca(2+) sensitivity of the myofilaments. Vascular diameter, myogenic tone, cytosolic Ca(2+), and Ca(2+) sensitivity were evaluated in pressurized SMA segments isolated from male and female gerbils using laser-scanning microscopy and microfluorometry. The gender difference of the LNNA-induced tone was compared, in the same vessel segments, to tone induced by 150 mM K(+) and endothelin-1, neither of which showed an apparent gender-difference. Interestingly, LNNA-induced tone in male SMAs was observed in protocols that included changes in intramural pressure, but not when the intramural pressure was held constant. LNNA in male SMAs did not increase the global Ca(2+) concentration in smooth muscle cells but increased the Ca(2+) sensitivity. This increase in the Ca(2+) sensitivity was abolished in the presence of the guanylyl cyclase inhibitor ODQ or by extrinsic application of either the nitric oxide (NO)-donor DEA-NONOate or the cGMP analog 8-pCPT-cGMP. The rho-kinase blocker Y27632 decreased the basal Ca(2+) sensitivity and abolished the LNNA-induced increase in Ca(2+) sensitivity in male SMAs. Neither LNNA nor Y27632 changed the Ca(2+) sensitivity in female SMAs. The data suggest that the gender difference in LNNA-induced tone is based on a gender difference in the regulation of rho-kinase mediated Ca(2+) sensitivity. Rho-kinase and NO thus emerge as critical factors in the regulation of cochlear blood flow. The larger role of NO-dependent mechanisms in male SMAs predicts greater restrictions on cochlear blood flow under conditions of impaired endothelial cell function. Public Library of Science 2013-01-03 /pmc/articles/PMC3536759/ /pubmed/23301097 http://dx.doi.org/10.1371/journal.pone.0053655 Text en © 2013 Reimann et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Reimann, Katrin
Krishnamoorthy, Gayathri
Wangemann, Philine
NOS Inhibition Enhances Myogenic Tone by Increasing Rho-Kinase Mediated Ca(2+) Sensitivity in the Male but Not the Female Gerbil Spiral Modiolar Artery
title NOS Inhibition Enhances Myogenic Tone by Increasing Rho-Kinase Mediated Ca(2+) Sensitivity in the Male but Not the Female Gerbil Spiral Modiolar Artery
title_full NOS Inhibition Enhances Myogenic Tone by Increasing Rho-Kinase Mediated Ca(2+) Sensitivity in the Male but Not the Female Gerbil Spiral Modiolar Artery
title_fullStr NOS Inhibition Enhances Myogenic Tone by Increasing Rho-Kinase Mediated Ca(2+) Sensitivity in the Male but Not the Female Gerbil Spiral Modiolar Artery
title_full_unstemmed NOS Inhibition Enhances Myogenic Tone by Increasing Rho-Kinase Mediated Ca(2+) Sensitivity in the Male but Not the Female Gerbil Spiral Modiolar Artery
title_short NOS Inhibition Enhances Myogenic Tone by Increasing Rho-Kinase Mediated Ca(2+) Sensitivity in the Male but Not the Female Gerbil Spiral Modiolar Artery
title_sort nos inhibition enhances myogenic tone by increasing rho-kinase mediated ca(2+) sensitivity in the male but not the female gerbil spiral modiolar artery
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3536759/
https://www.ncbi.nlm.nih.gov/pubmed/23301097
http://dx.doi.org/10.1371/journal.pone.0053655
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