{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T00:20:30Z","timestamp":1771374030425,"version":"3.50.1"},"reference-count":32,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Hypertension"],"published-print":{"date-parts":[[1999,2]]},"abstract":"<jats:p><jats:italic>Abstract<\/jats:italic>\u2014We investigated the involvement of actions mediated by endothelin-A (ET<jats:sub>A<\/jats:sub>) and endothelin-B (ET<jats:sub>B<\/jats:sub>) receptors in the pathogenesis of deoxycorticosterone acetate (DOCA)\u2013salt\u2013induced hypertension in rats. Two weeks after the start of DOCA-salt treatment, rats were given ABT-627 (10 [mg\/kg]\/d), a selective ET<jats:sub>A<\/jats:sub>receptor antagonist; A-192621 (30 [mg\/kg]\/d), a selective ET<jats:sub>B<\/jats:sub>receptor antagonist; or their vehicle for 2 weeks. Uninephrectomized rats without DOCA-salt treatment served as controls. Treatment with DOCA and salt for 2 weeks led to a mild but significant hypertension; in vehicle-treated DOCA-salt rats, systolic blood pressure increased markedly after 3 to 4 weeks. Daily administration of ABT-627 for 2 weeks almost abolished any further increases in blood pressure, whereas A-192621 did not affect the development of DOCA-salt\u2013induced hypertension. When the degree of vascular hypertrophy of the aorta was histochemically evaluated at 4 weeks, there were significant increases in wall thickness, wall area, and wall-to-lumen ratio in vehicle-treated DOCA-salt rats compared with uninephrectomized control rats. The development of vascular hypertrophy was markedly suppressed by ABT-627. In contrast, treatment with A-192621 significantly exaggerated these vascular changes. In vehicle-treated DOCA-salt rats, renal blood flow and creatinine clearance decreased, and urinary excretion of protein, blood urea nitrogen, fractional excretion of sodium, and urinary<jats:italic>N<\/jats:italic>-acetyl-\u03b2-glucosaminidase activity increased. Such damage was overcome by treatment with ABT-627 but not with A-192621; indeed, the latter agent led to worsening of the renal dysfunction. Histopathologic examination of the kidney in vehicle-treated DOCA-salt rats revealed tubular dilatation and atrophy as well as thickening of small arteries. Such damage was reduced in animals given ABT-627, whereas more severe histopathologic changes were observed in A-192621\u2013treated animals. These results strongly support the view that ET<jats:sub>A<\/jats:sub>receptor\u2013mediated action plays an important role in the pathogenesis of DOCA-salt\u2013induced hypertension. On the other hand, it seems likely that the ET<jats:sub>B<\/jats:sub>receptor\u2013mediated action protects against vascular and renal injuries in this model of hypertension. A selective ET<jats:sub>A<\/jats:sub>receptor antagonist is likely to be useful for treatment of subjects with mineralocorticoid-dependent hypertension, whereas ET<jats:sub>B<\/jats:sub>-selective antagonism alone is detrimental to such cases.<\/jats:p>","DOI":"10.1161\/01.hyp.33.2.759","type":"journal-article","created":{"date-parts":[[2012,6,12]],"date-time":"2012-06-12T00:53:46Z","timestamp":1339462426000},"page":"759-765","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":79,"title":["Different Contributions of Endothelin-A and Endothelin-B Receptors in the Pathogenesis of Deoxycorticosterone Acetate\u2013Salt\u2013Induced Hypertension in Rats"],"prefix":"10.1161","volume":"33","author":[{"given":"Yasuo","family":"Matsumura","sequence":"first","affiliation":[{"name":"From the Department of Pharmacology, Osaka University of Pharmaceutical Sciences, Nasahara, Takatsuki, Osaka, Japan, and the Diabetes and Vascular Research Division (T.J.O.), Abbott Laboratories, Abbott Park, Ill."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Norio","family":"Hashimoto","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology, Osaka University of Pharmaceutical Sciences, Nasahara, Takatsuki, Osaka, Japan, and the Diabetes and Vascular Research Division (T.J.O.), Abbott Laboratories, Abbott Park, Ill."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shima","family":"Taira","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology, Osaka University of Pharmaceutical Sciences, Nasahara, Takatsuki, Osaka, Japan, and the Diabetes and Vascular Research Division (T.J.O.), Abbott Laboratories, Abbott Park, Ill."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toshihiko","family":"Kuro","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology, Osaka University of Pharmaceutical Sciences, Nasahara, Takatsuki, Osaka, Japan, and the Diabetes and Vascular Research Division (T.J.O.), Abbott Laboratories, Abbott Park, Ill."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rika","family":"Kitano","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology, Osaka University of Pharmaceutical Sciences, Nasahara, Takatsuki, Osaka, Japan, and the Diabetes and Vascular Research Division (T.J.O.), Abbott Laboratories, Abbott Park, Ill."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mamoru","family":"Ohkita","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology, Osaka University of Pharmaceutical Sciences, Nasahara, Takatsuki, Osaka, Japan, and the Diabetes and Vascular Research Division (T.J.O.), Abbott Laboratories, Abbott Park, Ill."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Terry J.","family":"Opgenorth","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology, Osaka University of Pharmaceutical Sciences, Nasahara, Takatsuki, Osaka, Japan, and the Diabetes and Vascular Research Division (T.J.O.), Abbott Laboratories, Abbott Park, Ill."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masanori","family":"Takaoka","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology, Osaka University of Pharmaceutical Sciences, Nasahara, Takatsuki, Osaka, Japan, and the Diabetes and Vascular Research Division (T.J.O.), Abbott Laboratories, Abbott Park, Ill."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1161\/hyp.25.6.1135"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.hyp.24.2.183"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1254\/jjp.70.313"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.hyp.21.3.294"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.hyp.21.6.916"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1995.tb13292.x"},{"key":"e_1_3_2_7_2","doi-asserted-by":"crossref","unstructured":"Kassab S Novak J Miller T Kirchner K Granger JP. 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