Chronic dietary L-arginine down-regulates adenosine receptor and nitric oxide synthase expression in rat heart

Rose'Meyer, Roselyn B., Harrison, Glenn J., Fenning, Andrew, Jenner, Tamsin L., 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.

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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 Nϖ-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 ID: 26785
Item Type: Article (Research - C1)
ISSN: 1742-7843
Date Deposited: 24 Apr 2013 11:17
FoR Codes: 06 BIOLOGICAL SCIENCES > 0601 Biochemistry and Cell Biology > 060110 Receptors and Membrane Biology @ 30%
11 MEDICAL AND HEALTH SCIENCES > 1115 Pharmacology and Pharmaceutical Sciences > 111501 Basic Pharmacology @ 30%
11 MEDICAL AND HEALTH SCIENCES > 1116 Medical Physiology > 111603 Systems Physiology @ 40%
SEO Codes: 97 EXPANDING KNOWLEDGE > 970111 Expanding Knowledge in the Medical and Health Sciences @ 50%
92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920103 Cardiovascular System and Diseases @ 50%
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