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.