{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T10:51:46Z","timestamp":1791888706246,"version":"4.3.4"},"reference-count":43,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2004,7,29]],"date-time":"2004-07-29T00:00:00Z","timestamp":1091059200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Acta Physiologica Scandinavica"],"published-print":{"date-parts":[[2004,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>In the kidney, cyclooxygenase\u20102 (COX\u20102) is expressed in the macula densa\/cTALH and medullary interstitial cells. The macula densa is involved in regulating afferent arteriolar tone and renin release by sensing alterations in luminal chloride via changes in the rate of Na<jats:sup>+<\/jats:sup>\/K<jats:sup>+<\/jats:sup>\/2Cl<jats:sup>\u2212<\/jats:sup> cotransport, and administration of non\u2010specific cyclooxygenase inhibitors will blunt increases in renin release mediated by macula densa sensing of decreases in luminal NaCl. High renin states [salt deficiency, angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers, diuretic administration or experimental renovascular hypertension] are associated with increased macula densa\/cTALH COX\u20102 expression. Furthermore, there is evidence that angiotensin II and\/or aldosterone may inhibit COX\u20102 expression. In AT1 receptor knockout mice, COX\u20102 expression is increased similar to increases with ACE inhibitors or AT1 receptor blockers. Direct administration of angiotensin II inhibits macula densa COX\u20102 expression. Previous studies demonstrated that alterations in intraluminal chloride concentration are the signal for macula densa regulation of tubuloglomerular feedback and renin secretion, with high chloride stimulating tubuloglomerular feedback and low chloride stimulating renin release. When cultured cTALH or macula densa cells were incubated in media with selective substitution of chloride ions, COX\u20102 expression and prostaglandin production were significantly increased. A variety of studies have indicated a role for COX\u20102 in the macula densa mediation of renin release. In isolated perfused glomerular preparations, renin release induced by macula densa perfusion with a low chloride solution was inhibited by a COX\u20102 inhibitor but not a COX\u20101 inhibitor. <jats:italic>In vivo<\/jats:italic> studies in rats indicated that increased renin release in response to low\u2010salt diet, ACE inhibitor, loop diuretics or aortic coarctation could be inhibited by administration of COX\u20102\u2010selective inhibitors. In mice with genetic deletion of COX\u20102, ACE inhibitors or low\u2010salt diet failed to increase renal renin expression, although renin significantly increased in wild type mice. In contrast, in COX\u20101 null mice there were no significant differences in either the basal or ACE inhibitor\u2010stimulated level of renal renin activity from plasma or renal tissue compared with wild type mice. In summary, there is increasing evidence that COX\u20102 expression in the macula densa and surrounding cortical thick ascending limb cells is regulated by angiotensin II and is a modulator of renal renin production. These interactions of COX\u20102 derived prostaglandins and the renin\u2013angiotensin system may underlie physiological and pathophysiological regulation of renal function.<\/jats:p>","DOI":"10.1111\/j.1365-201x.2004.01329.x","type":"journal-article","created":{"date-parts":[[2004,7,30]],"date-time":"2004-07-30T05:29:43Z","timestamp":1091165383000},"page":"543-547","source":"Crossref","is-referenced-by-count":81,"title":["Cyclooxygenase\u20102 and the renal renin\u2013angiotensin system"],"prefix":"10.1111","volume":"181","author":[{"given":"R. C.","family":"Harris","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.\u2010Z.","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.\u2010F.","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2004,7,29]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.2001.00072.x"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI5505"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI10318"},{"key":"e_1_2_5_5_1","doi-asserted-by":"crossref","first-page":"F449","DOI":"10.1152\/ajprenal.2001.280.3.F449","article-title":"Genetic deletion of COX\u20102 prevents increased renin expression in response to ACE inhibition","volume":"280","author":"Cheng H.F.","year":"2001","journal-title":"Am J Physiol Renal Physiol"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00150.2002"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/378406a0"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.9.6_Pt_2.III49"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/12.11.2215"},{"key":"e_1_2_5_10_1","first-page":"F18","article-title":"Cloning, expression, and regulation of rabbit cyclooxygenase\u20102 in renal medullary interstitial cells","volume":"273","author":"Guan Y.","year":"1997","journal-title":"Am J Physiol"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.29.1.297"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1097\/00004872-200018080-00016"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1097\/00004872-199607000-00003"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI117620"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.31.1.201"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.26.1.137"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00209.2001"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/ki.1997.449"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.2001.00988.x"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0009-9236(01)49789-X"},{"key":"e_1_2_5_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004240100616"},{"key":"e_1_2_5_22_1","doi-asserted-by":"publisher","DOI":"10.1177\/019262339802600116"},{"key":"e_1_2_5_23_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200008313430915"},{"key":"e_1_2_5_24_1","first-page":"F460","article-title":"Localization of cyclooxygenase\u20101 and \u20102 in adult and fetal human kidney: implication for renal function","volume":"272","author":"Komhoff M.","year":"1997","journal-title":"Am J Physiol"},{"key":"e_1_2_5_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0085-2538(15)46757-2"},{"key":"e_1_2_5_26_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.2000.00425.x"},{"key":"e_1_2_5_27_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00129.2001"},{"key":"e_1_2_5_28_1","first-page":"F186","article-title":"Characterization of the macula densa stimulus for renin secretion","volume":"259","author":"Lorenz J.N.","year":"1990","journal-title":"Am J Physiol"},{"key":"e_1_2_5_29_1","first-page":"F486","article-title":"Renin release from isolated juxtaglomerular apparatus depends on macula densa chloride transport","volume":"260","author":"Lorenz J.N.","year":"1991","journal-title":"Am J Physiol"},{"key":"e_1_2_5_30_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.16.3.261"},{"key":"e_1_2_5_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00374901"},{"key":"e_1_2_5_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(99)01088-1"},{"key":"e_1_2_5_33_1","first-page":"S39","article-title":"Macula densa cell function","volume":"32","author":"Persson A.E.","year":"1991","journal-title":"Kidney Int Suppl"},{"key":"e_1_2_5_34_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.2002.00435.x"},{"key":"e_1_2_5_35_1","first-page":"S51","article-title":"Chloride concentration in macula densa and cortical thick ascending limb cells","volume":"32","author":"Salomonsson M.","year":"1991","journal-title":"Kidney Int Suppl"},{"key":"e_1_2_5_36_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.1998.274.2.R263"},{"key":"e_1_2_5_37_1","first-page":"290","article-title":"Effect of selective inhibition of the inducible cyclooxygenase on renin release in healthy volunteers","volume":"46","author":"Stichtenoth D.O.","year":"1998","journal-title":"J Invest Med"},{"key":"e_1_2_5_38_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.1999.277.5.F706"},{"key":"e_1_2_5_39_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.34.1.96"},{"key":"e_1_2_5_40_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.34.3.503"},{"key":"e_1_2_5_41_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.1998.274.3.F481"},{"key":"e_1_2_5_42_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.2000.279.5.F819"},{"key":"e_1_2_5_43_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M006218200"},{"key":"e_1_2_5_44_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.26.15280"}],"container-title":["Acta Physiologica Scandinavica"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fj.1365-201X.2004.01329.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/j.1365-201X.2004.01329.x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,15]],"date-time":"2023-10-15T18:18:51Z","timestamp":1697393931000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/j.1365-201X.2004.01329.x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,7,29]]},"references-count":43,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2004,8]]}},"alternative-id":["10.1111\/j.1365-201X.2004.01329.x"],"URL":"https:\/\/doi.org\/10.1111\/j.1365-201x.2004.01329.x","archive":["Portico"],"relation":{},"ISSN":["0001-6772","1365-201X"],"issn-type":[{"value":"0001-6772","type":"print"},{"value":"1365-201X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2004,7,29]]}}}