Nitric oxide synthase expression in AT2 receptor–deficient mice after DOCA-salt.

Nitric oxide synthase expression in AT2 receptor–deficient mice after DOCA-salt. Background. Angiotensin II type 2 receptor–deficient mice (AT2−/y) provide an opportunity to study the relationship between the angiotensin II type 1 receptor (AT1) and nitric oxide synthase (NOS) isoforms without concomitant AT2 receptor–related effects. To test this relationship, the expression of renal NOS isoforms (neural, inducible, and endothelial) in AT2−/y and AT2+/y mice was examined. The mice were challenged with deoxycorticosterone acetate (DOCA)-salt to stimulate NO generation. Methods. Gene expression analyses by real-time polymerase chain reaction (PCR) (TaqMan) were performed in kidneys to characterize neuronal nitric oxide synthase (nNOS), epithelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS), and the AT1 receptor. Pressure-natriuresis experiments were done to determine the physiologic background. Results. AT2−/y mice showed nNOS and iNOS up-regulation. DOCA-salt increased iNOS expression more in AT2−/y mice than in AT2+/y mice. Immunohistochemistry localized the iNOS expression with DOCA-salt mainly in the glomeruli. eNOS was not different between the groups, and was not affected by DOCA-salt. DOCA-salt increased mean arterial pressure more in AT2−/y mice than in AT2+/y mice. Concomitantly, the pressure-natriuresis relationship was shifted to the right in AT2−/y and AT2+/y mice after DOCA-salt. DOCA-salt decreased renal blood flow (RBF) and glomerular filtration rate (GFR) in both groups. [ABSTRACT FROM AUTHOR]