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      Renoprotective Effects of Omapatrilat Are Mediated Partially by Bradykinin

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          Aim: To investigate the effects of omapatrilat on systemic and renal hemodynamics, glomerular dynamics, renal function, and histopathological changes as well as the participation of the bradykinin B2 receptor in WKY, SHR, and L-NAME/SHR rats. Methods: Eight groups of 17-week-old rats were examined using renal micropuncture techniques and histopathological analyses after 3 weeks of treatment: group 1, WKY control; group 2, WKY+omapatrilat (40 mg/kg/day); group 3, SHR control; group 4, SHR+omapatrilat; group 5, SHR+ L-NAME (50 mg/l); group 6, SHR+ L-NAME+omapatrilat; group 7, SHR+ L-NAME for 3 weeks followed by omapatrilat for a subsequent 3 weeks, and group 8, SHR+ L-NAME+omapatrilat+bradykinin antagonist icatibant (500 µg/kg/day). Results: In WKY and SHR, omapatrilat significantly reduced the mean arterial pressure, increased effective renal blood flow and single nephron plasma flow associated with reduced glomerular arteriolar resistances. Furthermore, omapatrilat prevented and reversed L-NAME induced urinary protein excretion, glomerular and arteriolar injuries, glomerular morphometric alterations, and glomerular apoptosis (at least, p < 0.05). Icatibant partially inhibited these beneficial effects of omapatrilat. Conclusion: Omapatrilat provided potent antihypertensive and renoprotective actions, which were mediated, in part, by bradykinin.

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          Most cited references 12

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          Nitric oxide induces and inhibits apoptosis through different pathways.

          Physiological levels of nitric oxide (NO) regulate vascular tone and protect the microvasculature from injury whereas excessive NO may be harmful. The present study explored the effects of NO on human endothelial cell apoptosis. We found that the NO donor S-nitroso-N-acetylpenicillamine (SNAP) inhibited TNFalpha-induced endothelial apoptosis and that this was mediated partly through the cGMP pathway. In contrast, high SNAP concentration induced endothelial apoptosis via cGMP-independent pathways and the cGMP pathway protected against NO-induced apoptosis. These findings demonstrate that low NO concentrations contribute to human endothelial cell survival, whereas higher NO concentrations are pathological and promote destruction of endothelial cells.
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            Comparison of vasopeptidase inhibitor, omapatrilat, and lisinopril on exercise tolerance and morbidity in patients with heart failure: IMPRESS randomised trial

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              Nitric Oxide Inhibits Apoptosis by Preventing Increases in Caspase-3-like Activity via Two Distinct Mechanisms


                Author and article information

                Am J Nephrol
                American Journal of Nephrology
                S. Karger AG
                August 2003
                31 July 2003
                : 23
                : 4
                : 214-221
                Hypertension Research Laboratories, Ochsner Clinic Foundation, New Orleans, La., USA
                71507 Am J Nephrol 2003;23:214–221
                © 2003 S. Karger AG, Basel

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                Page count
                Tables: 5, References: 47, Pages: 8
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                Original Article: Basic Sciences


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