{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,17]],"date-time":"2025-09-17T15:04:24Z","timestamp":1758121464644},"reference-count":21,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Hypertension"],"published-print":{"date-parts":[[2003,3]]},"abstract":"<jats:p>Long-term exposure of uninephrectomized rats to desoxycorticosterone acetate (DOCA)\/salt induces cardiac fibrosis and hypertrophy through mineralocorticoid receptors (MRs). However, the underlying cellular mechanisms remain unclear. To determine whether Na\/H exchange isoform 1 (NHE1) is involved in the cellular mechanisms, we examined the effects of a specific NHE1 inhibitor, cariporide, and an MR antagonist, spironolactone, on DOCA\/salt-induced cardiac fibrosis and hypertrophy. Uninephrectomized rats were given 20 mg of DOCA (single subcutaneous injection) plus 0.9% NaCl\/0.3% KCl to drink and were killed at 8 days. Two groups of rats given DOCA\/salt were treated with either spironolactone (50 mg\/kg per day SC) or cariporide (30 mg\/kg per day PO) for 8 days. Control rats were treated with only high salt after the operation. The DOCA\/salt-induced perivascular collagen deposition was completely abolished by cariporide and spironolactone. DOCA\/salt-induced interstitial collagen deposition was partially and completely suppressed by spironolactone and cariporide, respectively. The rats exposed to DOCA\/salt had cardiocyte hypertrophy in the subendocardial and subepicardial regions, a finding that was completely inhibited by cariporide but not by spironolactone. In rats given DOCA\/salt, NHE1 protein expression was markedly increased. This was partially and completely reversed by spironolactone and cariporide, respectively. We concluded that cardiac NHE1 contributes to DOCA\/salt-induced cardiac fibrosis and hypertrophy and that the NHE1 inhibitor cariporide completely prevents the detrimental effects of DOCA\/salt on the heart. We also demonstrated that DOCA\/salt-induced cardiac injury through the MRs partly occurs through NHE1 activation.<\/jats:p>","DOI":"10.1161\/01.hyp.0000056769.73726.e5","type":"journal-article","created":{"date-parts":[[2003,3,6]],"date-time":"2003-03-06T21:45:38Z","timestamp":1046987138000},"page":"493-498","update-policy":"http:\/\/dx.doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":35,"title":["Na\/H Exchange Isoform 1 Is Involved in Mineralocorticoid\/Salt-Induced Cardiac Injury"],"prefix":"10.1161","volume":"41","author":[{"given":"Genro","family":"Fujisawa","sequence":"first","affiliation":[{"name":"From the Divisions of Endocrinology and Metabolism and Nephrology, Department of Internal Medicine, Jichi Medical School, Minamikawachi, Tochigi, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Koji","family":"Okada","sequence":"additional","affiliation":[{"name":"From the Divisions of Endocrinology and Metabolism and Nephrology, Department of Internal Medicine, Jichi Medical School, Minamikawachi, Tochigi, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shigeaki","family":"Muto","sequence":"additional","affiliation":[{"name":"From the Divisions of Endocrinology and Metabolism and Nephrology, Department of Internal Medicine, Jichi Medical School, Minamikawachi, Tochigi, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nobuya","family":"Fujita","sequence":"additional","affiliation":[{"name":"From the Divisions of Endocrinology and Metabolism and Nephrology, Department of Internal Medicine, Jichi Medical School, Minamikawachi, Tochigi, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naoki","family":"Itabashi","sequence":"additional","affiliation":[{"name":"From the Divisions of Endocrinology and Metabolism and Nephrology, Department of Internal Medicine, Jichi Medical School, Minamikawachi, Tochigi, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eiji","family":"Kusano","sequence":"additional","affiliation":[{"name":"From the Divisions of Endocrinology and Metabolism and Nephrology, Department of Internal Medicine, Jichi Medical School, Minamikawachi, Tochigi, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shun","family":"Ishibashi","sequence":"additional","affiliation":[{"name":"From the Divisions of Endocrinology and Metabolism and Nephrology, Department of Internal Medicine, Jichi Medical School, Minamikawachi, Tochigi, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"e_1_3_1_1_2","first-page":"893","volume":"120","year":"1992","unstructured":"Brilla CG, Weber KT. 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