title: Expression and function of COX isoforms in renal medulla: evidence for regulation of salt sensitivity and blood pressure.
abstract: Expression of cyclooxygenase (COX)-2, but not COX-1, in the renal medulla is stimulated by chronic salt loading; yet the functional implication of this phenomenon is incompletely understood. The present study examined the cellular localization and antihypertensive function of high-salt-induced COX-2 expression in the renal medulla, with a parallel assessment of the function of COX-1. COX-2 protein expression in response to high-salt loading, assessed by immunostaining, was found predominantly in inner medullary interstitial cells, whereas COX-1 protein was abundant in collecting duct (CD) and inner medullary interstitial cells and was not affected by high salt. We compared mRNA expressions of COX-1 and COX-2 in CD vs. non-CD cells isolated from aquaporin 2-green fluorescent protein transgenic mice. A low level of COX-2 mRNA, but a high level of COX-1 mRNA, as determined by real-time RT-PCR, was detected in CD compared with non-CD segments. During high-salt intake, chronic infusions of the COX-2 blocker NS-398 and the COX-1 blocker SC-560 into the renal medulla of Sprague-Dawley rats for 5 days induced approximately 30- and 15-mmHg increases in mean arterial pressure, respectively. During similar high-salt intake, COX-1 knockout mice exhibited a gradual, but significant, increase in systolic blood pressure that was associated with a marked suppression of urinary PGE2 excretion. Therefore, we conclude that the two COX isoforms in the renal medulla play a similar role in the stabilization of arterial blood pressure during salt loading.
authors.affiliation: University of Utah, Bldg. 2, Research Service, Salt Lake City, UT 84148, USA.
authors.forename: Wenling
authors.initials: W
authors.lastname: Ye
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.forename: Elaine
authors.initials: E
authors.lastname: Hillas
authors.forename: Donald E
authors.initials: DE
authors.lastname: Kohan
authors.forename: R Lance
authors.initials: RL
authors.lastname: Miller
authors.forename: Raoul D
authors.initials: RD
authors.lastname: Nelson
authors.forename: Matthew
authors.initials: M
authors.lastname: Honeggar
authors.forename: Tianxin
authors.initials: T
authors.lastname: Yang
mesh_terms: D000818:Animals; D051399:Aquaporin 2 / Q000235:genetics; D001794:Blood Pressure / Q000187:drug effects*; D051545:Cyclooxygenase 1 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051546:Cyclooxygenase 2 / Q000378:metabolism / Q000502:physiology*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D007679:Kidney Medulla / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D009578:Nitrobenzenes / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D017673:Sodium Chloride, Dietary / Q000494:pharmacology*; D013449:Sulfonamides / Q000494:pharmacology
chemical_list: C496024:Aqp2 protein, mouse; D051399:Aquaporin 2; D016861:Cyclooxygenase Inhibitors; D008565:Membrane Proteins; D009578:Nitrobenzenes; D012333:RNA, Messenger; D017673:Sodium Chloride, Dietary; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496513:Ptgs1 protein, rat