EFFECTS OF HYPERCORTISOLEMIA OR HYPERINSULINEMIA ON NEUROCHEMICAL INDEXES OF CATECHOLAMINE RELEASE AND SYNTHESIS IN CONSCIOUS RATS

Glucocorticoids and insulin (INS) complexly affect sympathoneural and adrenomedullary outflows. This study assessed effects of chronic hyper cortisolemia and effects of INS independent of INS-induced hypoglycemi a on neurochemical indices of different aspects of catecholaminergic f unction in conscious rats. Since r-DOPA is the precursor of the endoge nous catecholamines and the immediate product of the rate-limiting enz ymatic step in catecholamine biosynthesis, alterations in rates of app earance (spillover) of L-DOPA in arterial plasma may reflect alteratio ns in catecholamine synthesis. The study therefore included examinatio n of whether cortisol (CORT) or INS affects L-DOPA spillover or renal excretion of dopamine (DA) derived from plasma L-DOPA. Arterial plasma levels and urinary excretion rates of endogenous catechols and radiol abelled L-DOPA and DA were measured during systemic intravenous infusi ons of [H-3]L-DOPA. CORT was administered via a subcutaneous minipump reservoir for one week prior to [H-3]L-DOPA infusion, and INS was infu sed with glucose to examine effects of hyperinsulinemia independently of hypoglycemia. CORT decreased plasma levels and urinary excretion of norepinephrine (NE). INS did not. Neither CORT nor INS affected level s of other catechols, L-DOPA spillover, or the rate of urinary excreti on of [H-3]DA for a given plasma level of [H-3]L-DOPA. The results sug gest that CORT inhibits sympathetically-mediated NE release without al tering overall rates of catecholamine turnover or synthesis in sympath etic nerves in vivo and that INS effects on catecholaminergic function depend entirely on INS-induced hypoglycemia.