Reduced inotropic heart response in selenium-deficient mice relates with inducible nitric oxide synthase

Abstract

Atria from mice fed a selenium-deficient (Se−) diet have a diminished β-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 β-adrenoceptor inotropic cardiac stimulation. Elevated nitric oxide levels may account for some of the pathophysiological effects of Se deficiency on the heart.