Vol. 284, Issue 2, H442-H448, February 2003
Reduced inotropic heart response in selenium-deficient mice
relates with inducible nitric oxide synthase
Ricardo M.
Gomez1,
Orville A.
Levander2, and
Leonor
Sterin-Borda1
1 Cátedra de Farmacología, Facultad de
Odontología, Universidad de Buenos Aires, Consejo Nacional
de Investigaciones Científicas y Técnicas de la
República Argentina, 1122 Buenos Aires,
Argentina; and 2 Beltsville Human Nutrition
Research Center, Department of Agriculture/Agricultural Research
Center, Beltsville, Maryland 20705
Atria from mice fed a selenium-deficient
(Se
) diet have a diminished 
-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
NG-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
-adrenoceptor inotropic cardiac stimulation. Elevated nitric oxide
levels may account for some of the pathophysiological effects of Se
deficiency on the heart.
antioxidants; cardiomyopathy; isoproterenol; Keshan disease
