Effects of hypercortisolemia or hyperinsulinemia on neurochemical indices of catecholamine release and synthesis in conscious rats.
Glucocorticoids and insulin (INS) complexly affect sympathoneural and adrenomedullary outflows. This study assessed effects of chronic hypercortisolemia and effects of INS independent of INS-induced hypoglycemia on neurochemical indices of different aspects of catecholaminergic function in conscious rats. Since L-DOPA is the precursor of the endogenous catecholamines and the immediate product of the rate-limiting enzymatic step in catecholamine biosynthesis, alterations in rates of appearance (spillover) of L-DOPA in arterial plasma may reflect alterations in catecholamine synthesis. The study therefore included examination 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 radiolabelled L-DOPA and DA were measured during systemic intravenous infusions of [3H]L-DOPA. CORT was administered via a subcutaneous minipump reservoir for one week prior to [3H]L-DOPA infusion, and INS was infused 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 levels of other catechols, L-DOPA spillover, or the rate of urinary excretion of [3H]DA for a given plasma level of [3H]L-DOPA. The results suggest that CORT inhibits sympathetically-mediated NE release without altering overall rates of catecholamine turnover or synthesis in sympathetic nerves in vivo and that INS effects on catecholaminergic function depend entirely on INS-induced hypoglycemia.
D000818:Animals; D001786:Blood Glucose / Q000502:physiology; D001923:Brain Chemistry / Q000502:physiology*; D002395:Catecholamines / Q000096:biosynthesis / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism; D004343:Drug Implants; D006854:Hydrocortisone / Q000097:blood / Q000502:physiology* / Q000652:urine; D006946:Hyperinsulinism / Q000097:blood / Q000503:physiopathology* / Q000652:urine; D007262:Infusions, Intravenous; D007328:Insulin / Q000097:blood; D007980:Levodopa / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D001786:Blood Glucose; D002395:Catecholamines; D004343:Drug Implants; D007328:Insulin; D007980:Levodopa; D004298:Dopamine; D006854:Hydrocortisone