{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,14]],"date-time":"2026-03-14T03:13:36Z","timestamp":1773458016573,"version":"3.50.1"},"reference-count":31,"publisher":"American Physiological Society","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Regulatory, Integrative and Comparative Physiology"],"published-print":{"date-parts":[[2005,6]]},"abstract":"<jats:p>The syndrome of apparent mineralocorticoid excess (SAME) is an autosomal recessive form of salt-sensitive hypertension caused by deficiency of the kidney type 2 11\u03b2-hydroxysteroid dehydrogenase (11\u03b2HSD2). In this disorder, cortisol is not inactivated by 11\u03b2HSD2, occupies mineralocorticoid receptors (MRs), and causes excessive sodium retention and hypertension. In renal medulla, prostaglandins derived from cyclooxygenase-2 (COX-2) stimulate sodium and water excretion, and renal medullary COX-2 expression increases after mineralocorticoid administration. We investigated whether medullary COX-2 also increases in rats with 11\u03b2HSD2 inhibition and examined its possible role in the development of hypertension. 11\u03b2HSD2 inhibition increased medullary and decreased cortical COX-2 expression in adult rats and induced high blood pressure in high-salt-treated rats. COX-2 inhibition had no effect on blood pressure in control animals but further increased blood pressure in high-salt-treated rats with 11\u03b2HSD2 inhibition. COX-1 inhibition had no effect on blood pressure in either control or experimental animals. 11\u03b2HSD2 inhibition also led to medullary COX-2 increase and cortical COX-2 decrease in weaning rats, primarily through activation of MRs. In the suckling rats, medullary COX-2 expression was very low, consistent with a urinary concentrating defect. 11\u03b2HSD2 inhibition had no effect on either cortical or medullary COX-2 expression in the suckling rats, consistent with low levels of circulating corticosterone in these animals. These data indicate that COX-2 plays a modulating role in the development of hypertension due to 11\u03b2HSD2 deficiency and that 11\u03b2HSD2 regulates renal COX-2 expression by preventing glucocorticoid access to MRs during postnatal development.<\/jats:p>","DOI":"10.1152\/ajpregu.00786.2004","type":"journal-article","created":{"date-parts":[[2005,2,18]],"date-time":"2005-02-18T01:24:08Z","timestamp":1108689848000},"page":"R1767-R1773","source":"Crossref","is-referenced-by-count":28,"title":["Interactions between 11\u03b2-hydroxysteroid dehydrogenase and COX-2 in kidney"],"prefix":"10.1152","volume":"288","author":[{"given":"Bing","family":"Yao","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raymond C.","family":"Harris","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ming-Zhi","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"24","reference":[{"key":"R1","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.36.2.187"},{"key":"R2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.16.9424"},{"key":"R3","doi-asserted-by":"crossref","unstructured":"Bostanjoglo M, Reeves WB, Reilly RF, Velazquez H, Robertson N, Litwack G, Morsing P, Dorup J, Bachmann S, and Ellison DH.11Beta-hydroxysteroid dehydrogenase, mineralocorticoid receptor, and thiazide-sensitive Na-Cl cotransporter expression by distal tubules.J Am Soc Nephrol9: 1347\u20131358, 1998.","DOI":"10.1681\/ASN.V981347"},{"key":"R4","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1991.260.2.C226"},{"key":"R5","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200422929"},{"key":"R6","doi-asserted-by":"publisher","DOI":"10.1126\/science.2845584"},{"key":"R7","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.1999.277.3.F352"},{"key":"R8","doi-asserted-by":"crossref","unstructured":"Harris RCand Breyer MD.Physiological regulation of cyclooxygenase-2 in the kidney.Am J Physiol Renal Physiol281: F1\u2013F11, 2001.","DOI":"10.1152\/ajprenal.2001.281.1.F1"},{"key":"R9","doi-asserted-by":"publisher","DOI":"10.1172\/JCI117620"},{"key":"R10","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0704821"},{"key":"R11","doi-asserted-by":"publisher","DOI":"10.1038\/ki.1997.449"},{"key":"R12","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-121-4-199408150-00011"},{"key":"R13","doi-asserted-by":"publisher","DOI":"10.1172\/JCI4445"},{"key":"R14","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00099.2003"},{"key":"R15","doi-asserted-by":"publisher","DOI":"10.1080\/07435809609043778"},{"key":"R16","doi-asserted-by":"publisher","DOI":"10.1038\/ng0895-394"},{"key":"R17","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-0760(98)00009-0"},{"key":"R18","doi-asserted-by":"publisher","DOI":"10.1172\/JCI0214752"},{"key":"R19","doi-asserted-by":"publisher","DOI":"10.1097\/00007890-200207150-00012"},{"key":"R20","doi-asserted-by":"publisher","DOI":"10.1210\/endo.138.2.4926"},{"key":"R21","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.0000129170.50448.5f"},{"key":"R22","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.1981.240.6.F471"},{"key":"R23","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.1998.00036.x"},{"key":"R24","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/17.5.753"},{"key":"R25","doi-asserted-by":"publisher","DOI":"10.1097\/00045391-200007030-00004"},{"key":"R26","doi-asserted-by":"crossref","unstructured":"Yang T, Singh I, Pham H, Sun D, Smart A, Schnermann JB, and Briggs JP.Regulation of cyclooxygenase expression in the kidney by dietary salt intake. 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