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L-arginine supplementation reduces cardiac noradrenergic neurotransmission in spontaneously hypertensive rats.

Lee CW, Li D, Channon KM, Paterson DJ - J. Mol. Cell. Cardiol. (2009)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology, Anatomy and Genetics, University of Oxford, UK.

ABSTRACT
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 mumol/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.

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SHR has lower atrial cGMP compared with WKY but this was increased with l-arg feeding. ⁎p < 0.05.
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fig2: SHR has lower atrial cGMP compared with WKY but this was increased with l-arg feeding. ⁎p < 0.05.

Mentions: We found that atrial cGMP was lower in the SHR control group compared with the WKY control group (2.4 ± 0.4 pmol/mg vs 4.4 ± 0.5 pmol/mg), but increased to 4.1 ± 0.5 pmol/mg protein (n = 10, p < 0.05) following l-arg oral supplementation (Fig. 2). We could not detect a significant difference in atrial cAMP levels among the groups (data not shown).


L-arginine supplementation reduces cardiac noradrenergic neurotransmission in spontaneously hypertensive rats.

Lee CW, Li D, Channon KM, Paterson DJ - J. Mol. Cell. Cardiol. (2009)

SHR has lower atrial cGMP compared with WKY but this was increased with l-arg feeding. ⁎p < 0.05.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2734311&req=5

fig2: SHR has lower atrial cGMP compared with WKY but this was increased with l-arg feeding. ⁎p < 0.05.
Mentions: We found that atrial cGMP was lower in the SHR control group compared with the WKY control group (2.4 ± 0.4 pmol/mg vs 4.4 ± 0.5 pmol/mg), but increased to 4.1 ± 0.5 pmol/mg protein (n = 10, p < 0.05) following l-arg oral supplementation (Fig. 2). We could not detect a significant difference in atrial cAMP levels among the groups (data not shown).

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology, Anatomy and Genetics, University of Oxford, UK.

ABSTRACT
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 mumol/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.

Show MeSH