Reduced inotropic heart response in selenium-deficient mice relates with inducible nitric oxide synthase.
Atria from mice fed a selenium-deficient (Se(-)) diet have a diminished beta-adrenoceptor-inotropic cardiac response to isoproterenol or norepinephrine compared with atria from mice fed the same diet supplemented with 0.2 mg/kg Se as sodium selenite (Se(+)). This diminished response could be reversed by feeding Se(-) mice the Se(+) diet for 1 wk or by pretreatment with nitric oxide synthase (NOS) inhibitors such as N(G)-monomethyl-l-arginine or aminopyridine. Elevated serum concentrations of nitrite/nitrate as well as a threefold increase in the atrial NOS activity were seen in the Se(-) versus Se(+) mice. Western blotting and indirect immunofluorescence indicated an enhanced expression of inducible NOS in hearts from Se(-) mice. Increased expression and activity of NOS and increased nitrite/nitrate levels from Se(-) mice correlated with an impaired response to beta-adrenoceptor inotropic cardiac stimulation. Elevated nitric oxide levels may account for some of the pathophysiological effects of Se deficiency on the heart.
Gomez
Ricardo M
RM
Cátedra de Farmacologia, Facultad de Odontología, Universidad de Buenos Aires, Consejo Nacional de Investigaciones Cientificas y Técnicas de la República Argentina, Argentina.
Levander
Orville A
OA
Sterin-Borda
Leonor
L
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000631:Aminopyridines / Q000494:pharmacology; D000818:Animals; D004032:Diet; D005260:Female; D006325:Heart Atria; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D051379:Mice; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology; D009206:Myocardium / Q000201:enzymology; D009566:Nitrates / Q000097:blood; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D009573:Nitrites / Q000097:blood; D009638:Norepinephrine / Q000494:pharmacology; D012643:Selenium / Q000008:administration & dosage / Q000172:deficiency* / Q000494:pharmacology; D019323:omega-N-Methylarginine / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D000318:Adrenergic beta-Agonists; D000631:Aminopyridines; D009566:Nitrates; D009573:Nitrites; D019323:omega-N-Methylarginine; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D012643:Selenium; D007545:Isoproterenol; D009638:Norepinephrine