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l-arginine supplementation reduces cardiac noradrenergic neurotransmission in spontaneously hypertensive rats
Spontaneously hypertensive rats (SHR) are known to have cardiac noradrenergic hyperactivity due to an impaired nitric oxide (NO)–cGMP pathway. We hypothesized that dietary l-arginine supplementation may correct this autonomic phenotype. Male SHR and Wistar Kyoto rats (WKY) aged 16–18 weeks were give...
Autores principales: | , , , |
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Formato: | Texto |
Lenguaje: | English |
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Academic Press
2009
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2734311/ https://www.ncbi.nlm.nih.gov/pubmed/19362092 http://dx.doi.org/10.1016/j.yjmcc.2009.03.023 |
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author | Lee, Chee-Wan Li, Dan Channon, Keith M. Paterson, David J. |
author_facet | Lee, Chee-Wan Li, Dan Channon, Keith M. Paterson, David J. |
author_sort | Lee, Chee-Wan |
collection | PubMed |
description | Spontaneously hypertensive rats (SHR) are known to have cardiac noradrenergic hyperactivity due to an impaired nitric oxide (NO)–cGMP pathway. We hypothesized that dietary l-arginine supplementation may correct this autonomic phenotype. Male SHR and Wistar Kyoto rats (WKY) aged 16–18 weeks were given l-arginine (10 g/L in drinking water) for 1 week. Separate control groups received no supplementation. The SHR control had a significantly lower plasma l-arginine than WKY control, but this was increased to a comparable level following l-arginine. Atrial cGMP was lower in the SHR control compared with the WKY control (2.4 ± 0.4 pmol/mg vs 3.9 ± 0.5 pmol/mg, p < 0.05), but increased to 4.1 ± 0.5 pmol/mg protein (n = 8, p < 0.05) with l-arginine. Evoked [(3)H]norepinephrine release in isolated spontaneously beating right atria from the SHR control (328 ± 19%, n = 19) was 28% higher than the WKY control (256 ± 20%, n = 14, p < 0.05), but was reduced to 258 ± 11% with l-arginine feeding (n = 24, p < 0.01). Soluble guanylyl cyclase (sGC) inhibition caused a greater increase of evoked norepinephrine release in the l-arginine fed SHR compared with the non-fed SHR. l-arginine feeding did not reduce evoked norepinephrine release in the WKY. In-vitro heart rate response to exogenous norepinephrine (0.1–5 μmol/L) was similar between l-arginine fed (n = 13) and non-fed SHR (n = 10), suggesting that l-arginine supplementation worked pre-synaptically. Myocardial tyrosine hydroxylase protein was decreased in SHR following l-arginine supplementation, providing a link to reduced synthesis of norepinephrine. In conclusion, l-arginine supplementation corrects local cardiac noradrenergic hyperactivity in the SHR, probably via increased pre-synaptic substrate availability of NOS–sGC–cGMP pathway and reduced tyrosine hydroxylase levels. |
format | Text |
id | pubmed-2734311 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
publisher | Academic Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-27343112009-08-28 l-arginine supplementation reduces cardiac noradrenergic neurotransmission in spontaneously hypertensive rats Lee, Chee-Wan Li, Dan Channon, Keith M. Paterson, David J. J Mol Cell Cardiol Original Article Spontaneously hypertensive rats (SHR) are known to have cardiac noradrenergic hyperactivity due to an impaired nitric oxide (NO)–cGMP pathway. We hypothesized that dietary l-arginine supplementation may correct this autonomic phenotype. Male SHR and Wistar Kyoto rats (WKY) aged 16–18 weeks were given l-arginine (10 g/L in drinking water) for 1 week. Separate control groups received no supplementation. The SHR control had a significantly lower plasma l-arginine than WKY control, but this was increased to a comparable level following l-arginine. Atrial cGMP was lower in the SHR control compared with the WKY control (2.4 ± 0.4 pmol/mg vs 3.9 ± 0.5 pmol/mg, p < 0.05), but increased to 4.1 ± 0.5 pmol/mg protein (n = 8, p < 0.05) with l-arginine. Evoked [(3)H]norepinephrine release in isolated spontaneously beating right atria from the SHR control (328 ± 19%, n = 19) was 28% higher than the WKY control (256 ± 20%, n = 14, p < 0.05), but was reduced to 258 ± 11% with l-arginine feeding (n = 24, p < 0.01). Soluble guanylyl cyclase (sGC) inhibition caused a greater increase of evoked norepinephrine release in the l-arginine fed SHR compared with the non-fed SHR. l-arginine feeding did not reduce evoked norepinephrine release in the WKY. In-vitro heart rate response to exogenous norepinephrine (0.1–5 μmol/L) was similar between l-arginine fed (n = 13) and non-fed SHR (n = 10), suggesting that l-arginine supplementation worked pre-synaptically. Myocardial tyrosine hydroxylase protein was decreased in SHR following l-arginine supplementation, providing a link to reduced synthesis of norepinephrine. In conclusion, l-arginine supplementation corrects local cardiac noradrenergic hyperactivity in the SHR, probably via increased pre-synaptic substrate availability of NOS–sGC–cGMP pathway and reduced tyrosine hydroxylase levels. Academic Press 2009-07 /pmc/articles/PMC2734311/ /pubmed/19362092 http://dx.doi.org/10.1016/j.yjmcc.2009.03.023 Text en © 2009 Elsevier Ltd. https://creativecommons.org/licenses/by/3.0/ Open Access under CC BY 3.0 (https://creativecommons.org/licenses/by/3.0/) license |
spellingShingle | Original Article Lee, Chee-Wan Li, Dan Channon, Keith M. Paterson, David J. l-arginine supplementation reduces cardiac noradrenergic neurotransmission in spontaneously hypertensive rats |
title | l-arginine supplementation reduces cardiac noradrenergic neurotransmission in spontaneously hypertensive rats |
title_full | l-arginine supplementation reduces cardiac noradrenergic neurotransmission in spontaneously hypertensive rats |
title_fullStr | l-arginine supplementation reduces cardiac noradrenergic neurotransmission in spontaneously hypertensive rats |
title_full_unstemmed | l-arginine supplementation reduces cardiac noradrenergic neurotransmission in spontaneously hypertensive rats |
title_short | l-arginine supplementation reduces cardiac noradrenergic neurotransmission in spontaneously hypertensive rats |
title_sort | l-arginine supplementation reduces cardiac noradrenergic neurotransmission in spontaneously hypertensive rats |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2734311/ https://www.ncbi.nlm.nih.gov/pubmed/19362092 http://dx.doi.org/10.1016/j.yjmcc.2009.03.023 |
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