Nitric oxide synthase inhibition accelerates the pressor response to low-dose angiotensin II, exacerbates target organ damage, and induces renin escape

摘要: Abstract Because nitric oxide may attenuate both the pressor and cytotoxic effects of angiotensin II (Ang II), we investigated whether synthase (NOS) inhibition might accelerate slow effect Ang II, augment target organ damage. Using conscious, chronically catheterized rats, previously observed that low-dose (10 ng/kg/min) rapidly increased mean arterial pressure (MAP) by approximately 25 mm Hg. The MAP then remained at this level for 2 to 4 days, again during next 5 days a further Hg second plateau. In present study, 7 Nω-nitro- l -arginine methyl ester (L-NAME; 10 μg/kg/min) alone 16 When was added L-NAME, as much with alone, but continued increase until day 4, reaching plateau high reached only on 9 alone. half rats infused L-NAME + plasma renin escaped from II-induced suppression after duration study. On first urinary protein excretion cardiac troponin T increased, indicating early By end all treated developed tubulointerstitial glomerular injuries, fibrosis renal arteries, interstitial fibrosis. Target damage greater in escape than those which suppressed, minimal or Taken together, these findings suggest endogenous NO normally attenuates response several protects Under conditions reduced bioavailability, result endothelial insufficiency, relatively small changes circulating levels organs. Moreover, leading initiate vicious cycle elevated production, higher blood