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      Renoprotective Mechanisms of Angiotensin II Antagonism in Experimental Chronic Renal Failure


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          Aims: We investigated angiotensin II and nitric oxide-cGMP pathway in the development of hypertension and renal damage in chronic experimental nephritis. Methods: Rats with autoimmune nephritis were treated for 12 weeks with AT1 receptor antagonist L-158,809 and/or ACE inhibitor captopril given in drinking water. Blood pressure, urinary albumin, and urinary excretion of cGMP were measured. Renal density of ACE, AT1 and AT2 receptors was determined by quantitative in vitro autoradiography. Results: L-158,809, captopril, and their combination decreased blood pressure and normalised urinary albumin excretion rate in rats with nephritis. In L-158,809-treated rats, cGMP excretion was increased compared to the vehicle-treated nephritic group suggesting that the dysfunctional nitric oxide system may be activated by angiotensin antagonism. In nephritic rats, AT1 and AT2 receptor binding densities in renal medulla were decreased, cortical AT receptor expression remained unchanged. Following L-158,809 treatment, both AT1 and AT2 receptor binding was suppressed. Conclusion: Long-term blockade of AT1 receptors in chronic nephritis has beneficial effects both on albuminuria and blood pressure being as effective as ACE inhibition or their combination. The stimulatory effect of AT1 receptor antagonism on cGMP production was not mediated by AT2 receptor-dependent mechanisms suggesting that AT1 receptor blockade per se favours activation of humoral pathways that stimulate cGMP production and potentially contribute to renal protection in chronic nephritis.

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          Author and article information

          Kidney Blood Press Res
          Kidney and Blood Pressure Research
          S. Karger AG
          03 July 2002
          : 25
          : 2
          : 71-79
          aMinerva Foundation Institute for Medical Research; bDepartment of Bacteriology and Immunology, Haartman Institute, University of Helsinki; cDepartment of Physiology, University of Oulu; dDepartment of Medicine, Helsinki University Central Hospital, Helsinki, Finland
          63511 Kidney Blood Press Res 2002;25:71–79
          © 2002 S. Karger AG, Basel

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          Page count
          Figures: 3, Tables: 5, References: 36, Pages: 9
          Self URI (application/pdf): https://www.karger.com/Article/Pdf/63511
          Self URI (text/html): https://www.karger.com/Article/FullText/63511
          Self URI (journal page): https://www.karger.com/SubjectArea/Nephrology
          Original Paper

          Cardiovascular Medicine,Nephrology
          Renal failure,Angiotensin receptor,Angiotensin receptor antagonist,Angiotensin-converting enzyme,Nitric oxide,Nephritis,Cyclic GMP,Angiotensin II


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