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We characterized in conscious dogs the hemodynamic and hormonal effects of 4 weeks of feeding either the nitric oxide synthase inhibitor<jats:italic>N<\/jats:italic><jats:sup>\u03c9<\/jats:sup>-nitro-<jats:sc>l<\/jats:sc>-arginine (3 mg \u00b7 kg<jats:sup>\u22121<\/jats:sup>\u00b7 d<jats:sup>\u22121<\/jats:sup>) or the nitric oxide precursor<jats:sc>l<\/jats:sc>-arginine (0.3 mg \u00b7 kg<jats:sup>\u22121<\/jats:sup>\u00b7 d<jats:sup>\u22121<\/jats:sup>) during the evolution of two-kidney, one clip hypertension. Inhibition of nitric oxide production elicited a form of hypertension more severe than that produced in placebo-fed two-kidney, one clip dogs. The higher levels of blood pressure were accompanied by lower levels of plasma renin activity and lower angiotensin II concentrations. During the chronic phase of renovascular hypertension, the fall in blood pressure produced by acute systemic injections of lisinopril or losartan was significantly reduced in dogs given the nitric oxide inhibitor. In contrast, chronic administration of<jats:sc>l<\/jats:sc>-arginine had no effect on the magnitude of hypertension or on the increases in renin activity and hyperangiotensinemia associated with the evolution of renal hypertension. Likewise, the fall in blood pressure produced by pharmacological blockade of angiotensin II was not different from that recorded in untreated renal hypertensive dogs. The vasodilator component of the blood pressure response due to intravenous injections of angiotensin-(1-7) (1 to 100 nmol\/kg) was augmented in both untreated and<jats:sc>l<\/jats:sc>-arginine\u2013treated two-kidney, one clip hypertensive dogs, but was significantly attenuated in hypertensive dogs fed the nitric oxide synthase inhibitor. These experiments demonstrated an important contribution of nitric oxide in modulating the increased activity of the peripheral renin-angiotensin system during the evolution of renovascular hypertension. Furthermore, our data show that the evolution of this form of experimental renal hypertension is accompanied by a magnification of the vasodilator actions of angiotensin-(1-7). Activation of endothelium-derived relaxing factors and angiotensin-(1-7) mechanisms may act in synergy to buffer the increase in vascular resistance produced by chronic renal ischemia.<\/jats:p>","DOI":"10.1161\/01.hyp.25.4.796","type":"journal-article","created":{"date-parts":[[2012,6,12]],"date-time":"2012-06-12T00:24:03Z","timestamp":1339460643000},"page":"796-802","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":80,"title":["Angiotensin-(1-7) and Nitric Oxide Interaction in Renovascular Hypertension"],"prefix":"10.1161","volume":"25","author":[{"given":"Hidetomo","family":"Nakamoto","sequence":"first","affiliation":[{"name":"From the Hypertension Center and the Department of General Surgery, The Bowman Gray School of Medicine of Wake Forest University, Winston-Salem, NC."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlos M.","family":"Ferrario","sequence":"additional","affiliation":[{"name":"From the Hypertension Center and the Department of General Surgery, The Bowman Gray School of Medicine of Wake Forest University, Winston-Salem, NC."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stanley B.","family":"Fuller","sequence":"additional","affiliation":[{"name":"From the Hypertension Center and the Department of General Surgery, The Bowman Gray School of Medicine of Wake Forest University, Winston-Salem, NC."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David L.","family":"Robaczewski","sequence":"additional","affiliation":[{"name":"From the Hypertension Center and the Department of General Surgery, The Bowman Gray School of Medicine of Wake Forest University, Winston-Salem, NC."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric","family":"Winicov","sequence":"additional","affiliation":[{"name":"From the Hypertension Center and the Department of General Surgery, The Bowman Gray School of Medicine of Wake Forest University, Winston-Salem, NC."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard H.","family":"Dean","sequence":"additional","affiliation":[{"name":"From the Hypertension Center and the Department of General Surgery, The Bowman Gray School of Medicine of Wake Forest University, Winston-Salem, NC."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/S0031-6997(25)06663-3","volume":"43","year":"1991","unstructured":"Moncada S, Palmer RMJ, Higgs EA. 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