{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T19:56:16Z","timestamp":1786132576749,"version":"build-2736575974"},"reference-count":32,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","funder":[{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["P01 HL136267"],"award-info":[{"award-number":["P01 HL136267"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JASN"],"published-print":{"date-parts":[[2020,6]]},"abstract":"\n Significance Statement<\/jats:title>\n \n Hypertension often occurs before renal function deteriorates in patients with autosomal dominant polycystic kidney disease (ADPKD), but it is unknown whether polycystin-1, the\n Pkd1<\/jats:italic>\n gene product, itself contributes to ADPKD hypertension. The authors examined this in mice with nephron-specific disruption of the\n Pkd1<\/jats:italic>\n gene without renal cysts. Compared with control mice, these knockout mice manifested reduced BP, enhanced natriuresis, decreased expression of Na\n +<\/jats:sup>\n \/K\n +<\/jats:sup>\n \/2Cl\n \u2212<\/jats:sup>\n cotransporter isoform 2 (NKCC2) protein, and increased urinary PGE\n 2<\/jats:sub>\n excretion in response to a high salt diet. Blockade of cyclooxygenase-2 abolished the BP difference between Pkd1 knockout and control mice. These studies, apparently the first\n in vivo<\/jats:italic>\n studies to describe a potential physiologic role for nephron polycystin-1, suggest that nephron polycystin-1 deficiency\n per se<\/jats:italic>\n does not contribute to ADPKD-associated hypertension.\n <\/jats:p>\n <\/jats:sec>\n \n Background<\/jats:title>\n \n Hypertension often occurs before renal function deteriorates in autosomal dominant polycystic kidney disease (ADPKD). It is unknown whether the\n Pkd1<\/jats:italic>\n gene product polycystin-1\u2014the predominant causal factor in ADPKD\u2014itself contributes to ADPKD hypertension independent of cystogenesis.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n We induced nephron-specific disruption of the\n Pkd1<\/jats:italic>\n gene in 3-month-old mice and examined them at 4\u20135 months of age.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Kidneys from the Pkd1 knockout mice showed no apparent renal cysts, tubule dilation, or increased cell proliferation. Compared with control mice, Pkd1 knockout mice exhibited reduced arterial pressure during high salt intake; this associated with an increased natriuretic, diuretic, and kaliuretic response during the first 2\u20133 days of salt loading. The lower arterial pressure and enhanced natriuresis during high salt loading in Pkd1 knockout mice were associated with lower urinary nitrite\/nitrate excretion and markedly increased urinary PGE\n 2<\/jats:sub>\n excretion, whereas GFR, plasma renin concentration, and urinary endothelin-1 excretion were similar between knockout and control mice. Kidney cyclooxygenase-2 protein levels were increased in Pkd1 knockout mice during high salt intake; administration of NS-398, a selective cyclooxygenase-2 inhibitor, abolished the arterial pressure difference between the knockout and control mice during high salt intake. Total kidney Na\n +<\/jats:sup>\n \/K\n +<\/jats:sup>\n \/2Cl\n \u2212<\/jats:sup>\n cotransporter isoform 2 (NKCC2) levels were greatly reduced in Pkd1 knockout mice fed a high salt diet compared with controls.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n These studies suggest that nephron polycystin-1 deficiency does not itself contribute to ADPKD hypertension and that it may, in fact, exert a relative salt-wasting effect. The work seems to comprise the first\n in vivo<\/jats:italic>\n studies to describe a potential physiologic role for nephron polycystin-1 in the absence of cysts, tubule dilation, or enhanced cell proliferation.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1681\/asn.2019090934","type":"journal-article","created":{"date-parts":[[2020,4,16]],"date-time":"2020-04-16T14:35:29Z","timestamp":1587047729000},"page":"1243-1254","source":"Crossref","is-referenced-by-count":7,"title":["Nephron-Specific Disruption of Polycystin-1 Induces Cyclooxygenase-2\u2013Mediated Blood Pressure Reduction Independent of Cystogenesis"],"prefix":"10.1681","volume":"31","author":[{"given":"Jayalakshmi","family":"Lakshmipathi","sequence":"first","affiliation":[{"name":"Division of Nephrology, University of Utah Health Center, Salt Lake City, Utah"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Gao","sequence":"additional","affiliation":[{"name":"Division of Nephrology, University of Utah Health Center, Salt Lake City, Utah"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunyan","family":"Hu","sequence":"additional","affiliation":[{"name":"Division of Nephrology, University of Utah Health Center, Salt Lake City, Utah"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah","family":"Stuart","sequence":"additional","affiliation":[{"name":"Division of Nephrology, University of Utah Health Center, Salt Lake City, Utah"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Genzen","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Utah Health Center, Salt Lake City, Utah"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nirupama","family":"Ramkumar","sequence":"additional","affiliation":[{"name":"Division of Nephrology, University of Utah Health Center, Salt Lake City, Utah"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donald E.","family":"Kohan","sequence":"additional","affiliation":[{"name":"Division of Nephrology, University of Utah Health Center, Salt Lake City, Utah"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2020,4,16]]},"reference":[{"key":"B1-20230819","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1038\/ki.1988.233","article-title":"Hypertension in autosomal dominant polycystic kidney disease","volume":"34","author":"Bell","year":"1988","journal-title":"Kidney Int"},{"key":"B2-20230819","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1053\/j.ackd.2010.01.001","article-title":"Hypertension in autosomal dominant polycystic kidney disease","volume":"17","author":"Chapman","year":"2010","journal-title":"Adv Chronic Kidney Dis"},{"key":"B3-20230819","doi-asserted-by":"crossref","first-page":"253","DOI":"10.4103\/1319-2442.202774","article-title":"Update on pathogenesis, management, and treatment of hypertension in 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