Rose'Meyer, Roselyn and Harrison, Glenn and Fenning, Andrew and Jenner, Tamsin and Brown, Lindsay (2008) Chronic dietary L-arginine down-regulates adenosine receptor and nitric oxide synthase expression in rat heart. Basic and Clinical Pharmacology and Toxicology, 102 (5). pp. 459-465. ISSN 1742-7835
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Identification Number or DOI: doi: 10.1111/j.1742-7843.2008.00209.x
L-Arginine increases myocardial nitric oxide production. Nitric oxide mediates many of the cardiovascular actions of adenosine and modulates adenosine metabolism. In this study, we examined the effect of chronic l-arginine (5%) intake on cardiac nitric oxide synthase (NOS) and adenosine receptor expression and cardiac function in rat Langendorff-isolated perfused hearts. Our results show that 4-week chronic l-arginine ingestion increases the weight of rat hearts by 17.6% (P < 0.05). l-Arginine treatment decreased the expression of all the cardiac adenosine receptors, with reductions in adenosine A1 (20-fold), A2A (7.7-fold), A2B (76-fold) and A3 (25.6-fold) mRNA (P < 0.05). NOS expression was variably affected with no change in the expression of NOS1 and 4.2-fold down-regulation of NOS3 expression with chronic l-arginine treatment (P < 0.05). NOS2 was expressed in control tissues; however, in l-arginine-treated hearts the amount of NOS2 mRNA was reduced to non-detectable levels. Following chronic l-arginine treatment, an increase in coronary perfusion pressure was observed (P < 0.05). Purine efflux was used as an indicator of metabolic efficiency. l-Arginine did not alter catecholamine-induced purine efflux (P > 0.05); however, noradrenaline-mediated increases in contractility and myocardial oxygen consumption were reduced. Vasodilator responses to 5′-N-ethylcarboxamidoadenosine (NECA) were reduced in hearts from l-arginine-treated rats and the NOS inhibitor Nω-nitro-l-arginine methyl ester (3 μM) did not inhibit responses to NECA. In conclusion, 4-week dietary supplementation of l-arginine reduced the expression of cardiac adenosine receptors and NOSs with a subsequent decrease in noradrenaline-stimulated cardiac function and adenosine receptor-mediated coronary vasodilation.
|Item Type:||Article (Commonwealth Reporting Category C)|
|Additional Information:||Authors retain copyright.|
|Uncontrolled Keywords:||animal tissue; dietary intake; heart function; heart muscle contractility; heart muscle oxygen consumption; heart perfusion; heart weight; ingestion; isolated heart; perfusion pressure; protein expression; receptor down regulation; vasodilatation|
|Fields of Research (FOR2008):||11 Medical and Health Sciences > 1101 Medical Biochemistry and Metabolomics > 110107 Metabolic Medicine|
11 Medical and Health Sciences > 1111 Nutrition and Dietetics > 111199 Nutrition and Dietetics not elsewhere classified
11 Medical and Health Sciences > 1102 Cardiovascular Medicine and Haematology > 110201 Cardiology (incl. Cardiovascular Diseases)
|Socio-Economic Objective (SEO2008):||E Expanding Knowledge > 97 Expanding Knowledge > 970111 Expanding Knowledge in the Medical and Health Sciences|
|Deposited On:||05 Aug 2011 20:41|
|Last Modified:||20 Dec 2011 12:01|
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