RESUMO
Neuronal nitric oxide synthase (nNOS), which catalyzes the generation of nitric oxide (NO), is expressed by neuron subpopulations in the CNS. Nitric oxide is involved in neurotransmission and central glucose homeostasis. Our prior studies have shown that carotid body receptors participate in brain glucose regulation in vivo, and suggest the presence of a NO tonic mechanism in the solitary tract nucleus (STn). However, the role of NO within STn in glucose control remains unknown. In this study, we explored the potential regulatory role of NO on brain glucose retention induced by carotid body chemoreceptor anoxic stimulation with sodium cyanide (NaCN) which inhibits oxidative metabolism. Intracisternal infusions of nitroxidergic drugs before carotid chemoreceptor stimulation in anesthetized rats, elicited changes in nitrite concentration in plasma and hypothalamus-pituitary (H-P) tissue, as well as in gene expression of neuronal and inducible isoforms (nNOS and iNOS) in H-P tissue. The changes observed in above variables modified brain glucose retention in an opposite direction. When the NO donor, sodium nitroprusside (SNP), was given before carotid stimulation, nitrite concentration in plasma and H-P tissue, and gene expression of nNOS and iNOS in H-P tissue increased, whereas brain glucose retention decreased. In contrast, when the NOS inhibitor, Nomega-nitro-L-arginine methyl ester (L-NAME) was infused immediately before carotid chemoreceptor stimulation, nitrite levels and nNOS expression decreased in plasma and H-P tissue, whereas brain glucose retention increased. Anoxic stimulation by itself induced an increase in the expression of both genes studied. All these results indicate that de novo expression of the nNOS gene in H-P tissue may be critically involved in central glucose changes observed after anoxic carotid chemoreceptor stimulation in conjunction with NO.
Assuntos
Encéfalo/metabolismo , Células Quimiorreceptoras/metabolismo , Inibidores Enzimáticos/farmacologia , Glucose/metabolismo , Sistema Hipotálamo-Hipofisário/metabolismo , Óxido Nítrico/metabolismo , Cianeto de Sódio/farmacologia , Animais , Corpo Carotídeo/metabolismo , Hipotálamo/metabolismo , Óxido Nítrico Sintase Tipo I/antagonistas & inibidores , Óxido Nítrico Sintase Tipo I/genética , Óxido Nítrico Sintase Tipo I/metabolismo , Hipófise/metabolismo , RatosRESUMO
We have previously shown that stimulation of carotid body receptors (CBR) with sodium cyanide (NaCN) elicits a rapid hyperglycemic reflex. Here we explore whether the pituitary and adrenals, two glands involved in glucose homeostasis, are necessary for this reflex. Experiments were performed on anesthetized rats that were artificially ventilated. Measurements of hepatic venous-arterial glucose difference indicated that CBR stimulation with a bolus of 5 micrograms/100 g NaCN produced an immediate increase in the output of glucose by the liver. The same dose of NaCN failed to increase hepatic output of glucose in rats with bilateral adrenalectomy or in rats 1 wk after surgical removal of neurohypophysis. Reflex glucose output by the liver was maintained after adenohypophysectomy or in adrenalectomized rats after adrenal autotransplantation to epiploon. Measurements of epinephrine in plasma and in the grafted adrenal tissue showed that the adrenal autograft can store and secrete catecholamines Immunocytochemical observations indicated that the grafted adrenals retain medullary cells. These results indicate that neurohypophysis and adrenals are necessary for the hyperglycemic reflex initiated by CBR stimulation with NaCN and that the participation of these two organs in this reflex is probably humoral.