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Title: Angiotensin-(1-7) prevents development of severe hypertension and end-organ damage in spontaneously hypertensive rats treated with L-NAME
Authors: Benter, I.F.
Yousif, M.H.M.
Anim, J.T.
Cojocel, C.
Diz, D.I.
Keywords: Angiotensin II
Issue Date: Feb-2006
Publisher: American Journal of Physiology - Heart and Circulatory Physiology
Citation: Benter, I. F., Yousif, M. H. M., Anim, J. T., Cojocel, C., & Diz, D. I. (2006). Angiotensin-(1-7) prevents development of severe hypertension and end-organ damage in spontaneously hypertensive rats treated with L-NAME. American Journal of Physiology - Heart and Circulatory Physiology, 290(2), H684-H691. Link to full text:
Abstract: We examined the influence of chronic treatment with ANG-(1-7) on development of hypertension and end-organ damage in spontaneously hypertensive rats (SHR) chronically treated with the nitric oxide synthesis inhibitor L-NAME (SHR-L-NAME). L-NAME administered orally (80 mg/l) for 4 wk significantly elevated mean arterial pressure (MAP) compared with SHR controls drinking regular water (269 ± 10 vs. 196 ± 6 mmHg). ANG-(1-7) (24 μg·kg -1·h -1) or captopril (300 mg/l) significantly attenuated the elevation in MAP due to L-NAME (213 ± 7 and 228 ± 8 mmHg, respectively), and ANG-(1-7) + captopril completely reversed the L-NAME-dependent increase in MAP (193 ± 5 mmHg). L-NAME-induced increases in urinary protein were significantly lower in ANG-(1-7)-treated animals (226 ± 6 vs. 145 ± 12 mg/day). Captopril was more effective (96 ± 12 mg/day), and there was no additional effect of captopril + ANG-(1-7) (87 ± 5 mg/day). The abnormal vascular responsiveness to endothelin-1, carbachol, and sodium nitroprusside in perfused mesenteric vascular bed of SHR-L-NAME was improved by ANG-(1-7) or captopril, with no additive effect of ANG-(1-7) + captopril. In isolated perfused hearts, recovery of left ventricular function from 40 min of global ischemia was significantly better in ANG-(1-7)- or captopril-treated SHR-L-NAME, with additive effects of combined treatment. The beneficial effects of ANG-(1-7) on MAP and cardiac function were inhibited when indomethacin was administered with ANG-(1-7), but indomethacin did not reverse the protective effects on proteinuria or vascular reactivity. The protective effects of the ANG-(1-7) analog AVE-0991 were qualitatively comparable to those of ANG-(1-7) but were not improved over those of captopril alone. Thus, during reduced nitric oxide availability, ANG-(1-7) attenuates development of severe hypertension and end-organ damage; prostaglandins participate in the MAP-lowering and cardioprotective effects of ANG-(1-7); and additive effects of captopril + ANG-(1-7) on MAP, but not proteinuria or endothelial function, suggest common, as well as different, mechanisms of action for the two treatments. Together, the results provide further evidence of a role for ANG-(1-7) in protective effects of angiotensin-converting enzyme inhibition and suggest dissociation of factors influencing MAP and those influencing end-organ damage
ISSN: 03636135
Appears in Collections:Department of Pathology 9

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