Renin-angiotensin blockade improves renal cGMP production via non-AT2-receptor mediated mechanisms in hypertension-induced by chronic NOS inhibition in rat

BackgroundTo investigate the changes in the angiotensin II (Ang II) receptors and nitric oxide (NO)-cGMP pathway in the rat kidney after nitric oxide synthase (NOS) blockade.MethodsCaptopril, an angiotensin-converting enzyme (ACE) inhibitor, 20 mg/100 ml; and/or L-158,809 (an Ang II AT 1-receptor antagonist, 5 mg/100 ml) and L-NAME (NOS inhibitor, 50 mg/100 ml) were administered orally for 12 weeks. Blood pressure (BP), urinary albumin, urinary cGMP excretion, plasma ANP, and plasma renin activity were measured. In vitro autoradiography was used to locate the Ang II receptors in the kidney.ResultsCaptopril and L-158,809 treatments normalised BP and prevented the appearance of albuminuria in rats receiving L-NAME. Urinary cGMP excretion was significantly increased in L-158,809-treated rats compared with the non-treated group, suggesting that the dysfunctional NO system may be activated by the treatment. AT1 -receptor binding in the kidney was inhibited to about 40% of the control value after administration...