Losartan (DUP-753) blocks the natriuretic, kaliuretic and antidiuretic effect of intracerebroventricular injection of carbachol in water-loaded rats.
We determined the effect of intracerebroventricular (icv) administration of losartan, an angiotensin II (ANG II) subtype 1 receptor (AT1) antagonist, on icv carbachol-induced natriuresis, kaliuresis and antidiuresis in water-loaded male Holtzman rats (250-300 g) with a cannula implanted into the lateral ventricle (LV). The rats were water loaded with 5% of their body weight by gavage twice, with the second gavage one hour after the first. Carbachol (2 nmol in 1 microliter) was injected icv immediately after the second load. When losartan (DUP-753, 50 nmol in 1 microliter) was administered icv, it was given 3 min before carbachol. Previous icv treatment with losartan significantly reduced the icv carbachol-induced natriuresis (324 +/- 17 microEq/120 min), kaliuresis (103 +/- 15 microEq/120 min) and antidiuresis (13.5 +/- 2.1 ml/120 min) compared to the effects of previous icv injection of saline (Na+ excretion = 498 +/- 22 microEq/120 min; K+ excretion = 167 +/- 20 microEq/120 min; urine volume = 5.2 +/- 1.2 ml/120 min). These results, reported as means +/- SEM for 12 rats in each group, are consistent with the hypothesis that AT1 subtype receptors participate in the regulation of body electrolyte balance.
Saad
W A
WA
Departamento de Ciências Fisiológicas, Universidade Estadual Paulista, Araraquara, SP, Brasil.
Luiz
A C
AC
Camargo
L A
LA
Renzi
A
A
Menani
J V
JV
Saad
W A
WA
D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology*; D002217:Carbachol / Q000008:administration & dosage / Q000037:antagonists & inhibitors*; D004231:Diuresis / Q000187:drug effects*; D004326:Drinking; D007093:Imidazoles / Q000494:pharmacology*; D007276:Injections, Intraventricular; D019808:Losartan; D008297:Male; D009318:Natriuresis / Q000187:drug effects*; D011188:Potassium / Q000652:urine*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013777:Tetrazoles / Q000494:pharmacology*
D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D007093:Imidazoles; D013777:Tetrazoles; D002217:Carbachol; D019808:Losartan; D011188:Potassium