Chronic dietary L-arginine down-regulates adenosine receptor and nitric oxide synthase expression in rat heart.
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 A(1) (20-fold), A(2A) (7.7-fold), A(2B) (76-fold) and A(3) (25.6-fold) mRNA (P < 0.05). NOS expression was variably affected with no change in the expression of NOS(1) and 4.2-fold down-regulation of NOS(3) expression with chronic L-arginine treatment (P < 0.05). NOS(2) was expressed in control tissues; however, in L-arginine-treated hearts the amount of NOS(2) 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 N omega-nitro-L-arginine methyl ester (3 microM) 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.
Rose'Meyer
Roselyn B
RB
School of Medical Sciences, Griffith University, Gold Coast, Queensland, Australia. r.rosemeyer@griffith.edu.au
Harrison
Glenn J
GJ
Fenning
Andrew
A
Jenner
Tamsin L
TL
Brown
Lindsay
L
D000818:Animals; D001120:Arginine / Q000008:administration & dosage / Q000494:pharmacology*; D019587:Dietary Supplements; D015536:Down-Regulation; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar; D018047:Receptors, Purinergic P1 / Q000096:biosynthesis*
D018047:Receptors, Purinergic P1; D001120:Arginine; D019001:Nitric Oxide Synthase