Effect of intracerebroventricularly injected insulin on urinary sodium excretion by cerebroventricular streptozotocin-treated rats.
Recent evidence suggests that insulin may influence many brain functions. It is known that intracerebroventricular (icv) injection of nondiabetogenic doses of streptozotocin (STZ) can damage insulin receptor signal transduction. In the present study, we examined the functional damage to the brain insulin receptors on central mechanisms regulating glomerular filtration rate and urinary sodium excretion, over four periods of 30 min, in response to 3 microl insulin or 0.15 NaCl (vehicle) injected icv in STZ-treated freely moving Wistar-Hannover rats (250-300 g). The icv cannula site was visually confirmed by 2% Evans blue infusion. Centrally administered insulin (42.0 ng/ micro l) increased the urinary output of sodium (from 855.6 85.1 to 2055 310.6 delta%/min; N = 11) and potassium (from 460.4 100 to 669 60.8 delta%/min; N = 11). The urinary sodium excretion response to icv insulin microinjection was markedly attenuated by previous central STZ (100 micro g/3 micro l) administration (from 628 45.8 to 617 87.6 delta%/min; N = 5) or by icv injection of a dopamine antagonist, haloperidol (4 micro g/3 micro l) (from 498 +/- 39.4 to 517 +/- 73.2 delta%/min; N = 5). Additionally, insulin-induced natriuresis occurred by increased post-proximal tubule sodium rejection, despite an unchanged glomerular filtration rate. Excluding the possibility of a direct action of STZ on central insulin receptor-carrying neurons, the current data suggest that the insulin-sensitive response may be processed through dopaminergic D1 receptors containing neuronal pathways.
Macedo
R F
RF
Disciplina de Medicina Interna, Laborat rio Balanço Hidro-Salino, Núcleo de Medicina e Cirurgia Experimental, Departamento de Clínica Médica, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, Campinas, SP, Brasil.
Furlan
F C
FC
Marshall
P S
PS
Michelotto
J B
JB
Gontijo
J A R
JA
D000818:Animals; D000903:Antibiotics, Antineoplastic; D001921:Brain / Q000187:drug effects*; D005919:Glomerular Filtration Rate / Q000187:drug effects*; D007276:Injections, Intraventricular; D007279:Injections, Subcutaneous; D007328:Insulin / Q000008:administration & dosage*; D008297:Male; D009318:Natriuresis / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D011972:Receptor, Insulin / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects*; D013311:Streptozocin; D013997:Time Factors
D000903:Antibiotics, Antineoplastic; D007328:Insulin; D013311:Streptozocin; D011972:Receptor, Insulin