Acute intracerebroventricular insulin microinjection after nitric oxide synthase inhibition of renal sodium handling in rats.
The role of the central nervous system (CNS) in the control of hydrosaline homeostasis has been strikingly demonstrated by several studies. Recent and growing evidence suggests that insulin or a nonapeptide-derived from the C-terminus of the insulin beta-chain may influence many brain functions. However, there is little information on the insulin-activated neural pathways regulating urinary sodium excretion. Also, we examined the influence of nitric oxide synthase activity by chronic oral administration of N(omega)-nitro-l-arginine methyl ester (L-NAME), an inhibitor of nitric oxide (NO) synthesis, after previous i.c.v. administration of insulin to unanesthetized, unrestrained rats that were randomly assigned to one of seven separated groups: (a) i.c.v. 0.15 M NaCl-injected (n = 11) and i.c.v. 126 ng (n = 11) insulin-injected rats; (b) i.c.v. insulin-injected in systemic L-NAME-treated (n = 10) and vehicle-treated insulin-injected rats (n = 10); and (c) subcutaneously (SC) insulin-injected rats (n = 5). We showed that centrally administered insulin produced increase in the urinary output of sodium (from 0.15 M NaCl: 855.6 +/- 85.1 Delta%.min(-1) to 126 ng insulin: 2055 +/- 310.6 Delta%.min(-1)) and potassium (126 ng: from 0.15 M NaCl: 460.4 +/- 100 Delta%.min(-1) to 126 ng insulin: 669 +/- 60.8 Delta%.min(-1)). The urinary sodium excretion response to i.c.v. 126 ng insulin microinjection was significantly abolished by previous systemic treatment of animals with 15 mg/kg/day L-NAME (from vehicle + 126 ng insulin: 1935 +/- 258.3 Delta%. min(-1) to L-NAME + 126 ng insulin: 582.3 +/- 69.6 Delta%. min(-1)). In addition, we showed that insulin-induced natriuresis occurred by increasing post-proximal tubule sodium rejection (FEPP(Na)), despite an unchanged glomerular filtration rate (C(Cr)). The current data suggests the novel concept that CNS NO-dependent neural pathways may play an instrumental role on efferent insulin-sensitive nerve activity from periventricular region. Speculatively, it seems interesting to suggest that perhaps one of the efferent signals triggered by insulin in the CNS may be nitrergic in nature, and that defects in this efferent signal could result in insulin central resistance, inability of renal tubules to handle the hydro electrolyte balance and hypertension.
Furlan
Fabricio Cecanho
FC
Disciplina de Medicina Interna, Laboratório Balanço Hidro-Salino, Núcleo de Medicina e Cirurgia Experimental, Campinas, SP, Brazil.
Marshall
Priscila Silva
PS
Macedo
Ronaldo Ferreira
RF
Carvalheira
José Barreto
JB
Michelotto
João Batista
JB
Gontijo
José Antonio Rocha
JA
D000818:Animals; D004336:Drug Antagonism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005919:Glomerular Filtration Rate; D007276:Injections, Intraventricular; D007279:Injections, Subcutaneous; D007328:Insulin / Q000008:administration & dosage* / Q000097:blood; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D008845:Microinjections; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009318:Natriuresis / Q000187:drug effects* / Q000502:physiology; D026602:Nitrergic Neurons / Q000187:drug effects / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D052248:Nitric Oxide Synthase Type I; D051381:Rats; D017208:Rats, Wistar
D004791:Enzyme Inhibitors; D007328:Insulin; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat; D019331:NG-Nitroarginine Methyl Ester