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To assess the role of aldosterone in the development of pathologic changes in these rats, we implanted time-release pellets containing 200 mg of the mineralocorticoid receptor antagonist, spironolactone, into 14 SHRSP at 7.5 weeks of age. Eight SHRSP littermates received placebo pellets. Over the period of study (3 to 4 weeks), systolic blood pressure (SBP) was not different between the groups. Spironolactone did not enhance water and electrolyte excretion. All placebo-treated SHRSP developed marked proteinuria (150\u00b16 mg\/d) whereas in spironolactone-treated SHRSP, urinary protein excretion (UPE) averaged 39\u00b19 mg\/d (<jats:italic>P<\/jats:italic>&lt;.0001). In a second study to assess effects on survival, 6 SHRSP received spironolactone (10 mg\/kg\/d) and 6 received vehicle. All but one of the control rats displayed signs of stroke and died by 16 weeks of age, while the spironolactone-treated SHRSP remained asymptomatic through 19 weeks of age (<jats:italic>P<\/jats:italic>&lt;.03). At 16 weeks of age, spironolactone-treated SHRSP were severely hypertensive (247\u00b13 mm Hg), yet UPE remained at baseline levels. In contrast, preterminal UPE averaged 136\u00b113 mg\/d in control rats (<jats:italic>P<\/jats:italic>&lt;.0001). In both studies, histopathologic examination revealed a marked protective effect of spironolactone against the development of malignant nephrosclerotic and cerebrovascular lesions. These observations indicate a vascular and end organ protective effect of spironolactone in the absence of lowered blood pressure in saline-drinking SHRSP and are consistent with a major role for mineralocorticoids as hormonal mediators of vascular injury.<\/jats:p>","DOI":"10.1161\/01.hyp.31.1.451","type":"journal-article","created":{"date-parts":[[2012,6,12]],"date-time":"2012-06-12T00:53:46Z","timestamp":1339462426000},"page":"451-458","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":359,"title":["Mineralocorticoid Blockade Reduces Vascular Injury in Stroke-Prone Hypertensive Rats"],"prefix":"10.1161","volume":"31","author":[{"given":"Ricardo","family":"Rocha","sequence":"first","affiliation":[{"name":"From the Departments of Pharmacology (R.R., K.K., C.T.S.), Pathology (P.N.C.) and Pediatrics (A.Z.) at New York Medical College, Valhalla, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Praveen N.","family":"Chander","sequence":"additional","affiliation":[{"name":"From the Departments of Pharmacology (R.R., K.K., C.T.S.), Pathology (P.N.C.) and Pediatrics (A.Z.) at New York Medical College, Valhalla, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kavita","family":"Khanna","sequence":"additional","affiliation":[{"name":"From the Departments of Pharmacology (R.R., K.K., C.T.S.), Pathology (P.N.C.) and Pediatrics (A.Z.) at New York Medical College, Valhalla, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Zuckerman","sequence":"additional","affiliation":[{"name":"From the Departments of Pharmacology (R.R., K.K., C.T.S.), Pathology (P.N.C.) and Pediatrics (A.Z.) at New York Medical College, Valhalla, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"Charles T.","family":"Stier","sequence":"additional","affiliation":[{"name":"From the Departments of Pharmacology (R.R., K.K., C.T.S.), Pathology (P.N.C.) and Pediatrics (A.Z.) at New York Medical College, Valhalla, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM197203022860901"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.hyp.13.2.115"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/ajh\/4.8.680"},{"key":"e_1_3_2_4_2","doi-asserted-by":"crossref","first-page":"1410","DOI":"10.1016\/S0022-3565(25)11459-6","volume":"260","year":"1992","unstructured":"Stier CT Jr, Mahboubi K, DiPippo VA, Levine S, Chander PN. 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