Decreased beta-adrenoceptor chronotropic response in selenium-deficient mice: negative crosstalk between iNOS activity and cAMP accumulation.
With the aim to study if selenium (Se) deficiency affects the basal frequency and cardiac response to isoproterenol (ISO), mice were fed a Se-deficient diet (Se-) or the same diet supplemented with 0.2 ppm Se as sodium selenite (Se+) for 4 wk. Atria frequency, cyclic AMP (cAMP) accumulation, nitric oxide synthase (NOS) activity, and beta-adrenoceptor-binding assay were then examined. Results showed that Se-mice have both a reduction in atria frequency as well as in cAMP content but higher NOS activity levels either at basal or after ISO stimulation. These differences were suppressed by feeding Se-mice with a Se-supplemented diet for 1 wk or by inhibition of inducible nitric oxide synthase (iNOS). Alterations observed after ISO stimulation in atria of Se-mice were not related to a beta-adrenoceptor expression modification because specific radioligand-binding parameters in cardiac membranes from Se-mice and Se+ mice were similar. The reduced response on rate and cAMP in atria from Se-mice to direct adenylate cyclase (AC) stimulation by forskolin and the shifted upward levels present in 2-amino-4-methylpyridine-treated Se-mice is in agreement with a negative crosstalk between iNOS activity and AC activity in Se-mice.
Gómez
Ricardo M
RM
Cátedra de Farmacología, Facultad de Odontología, Universidad de Buenos Aires, Buenos Aires, 1122, Argentina.
Pacienza
Natalia
N
Schattner
Mirta
M
Habarta
Alejandra
A
Levander
Orville A
OA
Sterin-Borda
Leonor
L
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D000242:Cyclic AMP / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015536:Down-Regulation / Q000502:physiology*; D005260:Female; D006325:Heart Atria / Q000378:metabolism / Q000503:physiopathology; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D051379:Mice; D009200:Myocardial Contraction / Q000502:physiology*; D009569:Nitric Oxide / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D011897:Random Allocation; D011943:Receptors, Adrenergic, beta / Q000378:metabolism* / Q000502:physiology; D012643:Selenium / Q000172:deficiency*; D015854:Up-Regulation / Q000502:physiology
D000318:Adrenergic beta-Agonists; D011943:Receptors, Adrenergic, beta; D009569:Nitric Oxide; D000242:Cyclic AMP; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D012643:Selenium; D007545:Isoproterenol