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Abstract
To determine whether the nitric oxide (NO) system in the central nervous system (CNS) is involved in the peripheral metabolism of carbohydrate we injected NG-methyl-L,arginine (L-NMA), an inhibitor of NO synthase, into the third cerebral ventricle of unanesthetized, unrestrained rats and determined the plasma level of glucose. This intracerebroventricular (i.c.v.) injection of the drug increased the plasma level of glucose dose-dependently, whereas an intravenous (i.v.) injection had no effect. The hyperglycemia thus induced was suppressed by concomitant i.c.v. or prior i.v. administration of L-arginine. Concomitant administration of D-arginine did not affect hyperglycemia by L-NMA. The i.c.v. injection of 5 x 10-6 mol L-NMA increased plasma levels of glucose, epinephrine and norepinephrine, and serum levels of glucagon. However, plasma levels of insulin were unchanged, despite the presence of hyperglycemia. The hyperglycemia produced by L-NMA was completely inhibited by bilateral adrenalectomy. It was also inhibited by prior intraperitoneal injection of phentolamine, but not of propranolol or naloxone. Results suggest that L-NMA acts on the CNS to stimulate adrenal secretion of epinephrine and, subsequently, to elevate glucose levels in the peripheral blood. The NO system thus seems to be involved in the neural regulation of the adrenal by the GNS, which in turn regulates peripheral blood glucose levels.
Key Words
Nitric oxide
Catecholamines
Opioid peptides
Adrenal medulla
Glucose
Insulin
Glucagon
Glycemia
Introduction
Nitric oxide (NO), a major endothelium-derived relaxing factor, is synthesized enzymatically from L^arginine in the central nervous system (CNS) as well as other tissues [ 1-4]. Since it was first recognized to be a messenger molecule in the CNS by Garthwaite et al. [5] in 1988, NO has been shown to function as an important signal transduction system in the CNS. Rettori et al. [6] demonstrated that NG-methyl-L-arginine (L-NMA), a selective inhibitor of NO synthesis, blocked stimulation of prostaglandin-E2 release from hypothalamic fragments induced by norepinephrine, which in turn inhibited exocytosis of secretory granules of luteinizing-hormone-releasing hormone. Karanth et al. [7] showed that interleukin-2induced corticotropin-releasing-hormone (CRH) release from hypothalami was elevated by L-arginine, the NO precursor, and suppressed by L-NMA. On the other hand, Costa et al. [8] reported that interleukin-1 I-induced CRH release was inhibited by L-arginine and this inhibition was restored by the addition of L-NMA. In an in vivo study,...