title: Low plasma renin and reduced renin secretory responses to acute stimuli in conscious COX-2-deficient mice.
abstract: In the current experiments, we determined the response of plasma renin concentration (PRC) to acute intraperitoneal administration of furosemide (40 mg/kg), hydralazine (2 mg/kg), isoproterenol (10 mg/kg), candesartan (50 microg), or quinaprilate (50 microg) in conscious wild-type (WT) and cyclooxygenase (COX)-2-/- mice on three different genetic backgrounds (mixed, C57BL/6, 129J). PRC was measured in plasma obtained by tail vein puncture. Basal PRC was significantly lower in COX-2-/- than WT mice independent of genetic background (51, 10, and 17% of WT in mixed, 129J, and C57BL/6). All five acute interventions caused significant increases of PRC in both COX-2+/+ and -/- mice, but the response was consistently less in COX-2-deficient mice (e.g., DeltaPRC in ng ANG I x ml(-1) x h(-1) caused by furosemide, isoproterenol, hydralazine, quinaprilate, or candesartan 4,699 +/- 544, 3,534 +/- 957, 2,522 +/- 369, 9,453 +/- 1,705, 66,455 +/- 21,938 in 129J WT, and 201 +/- 78, 869 +/- 275, 140 +/- 71, 902 +/- 304, 2,660 +/- 954 in 129J COX-2-/-). A low-NaCl diet and enalapril for 1 wk caused a 14-fold elevation of PRC in COX-2-/- mice and was associated with a greatly increased PRC response to acute furosemide (DeltaPRC 201 +/- 78 before and 15,984 +/- 2,397 after low Na/enalapril). As measured by radiotelemetry, blood pressure and heart rate responses to furosemide, hydralazine, isoproterenol, candesartan, or quinaprilate were not different between COX-2 genotypes. In conclusion, chronic absence of COX-2 reduces renin expression, release, and PRC and is associated with a reduced ability to alter PRC during acute stimulation regardless of the nature of the stimulus. COX-2 activity does not appear to be a mandatory and specific requirement for furosemide-stimulated renin secretion.
authors.affiliation: National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bldg. 10, Rm. 4D51, 10 Center Drive-MSC 1370, Bethesda, MD 20892, USA.
authors.forename: Soo Mi
authors.initials: SM
authors.lastname: Kim
authors.forename: Limeng
authors.initials: L
authors.lastname: Chen
authors.forename: Diane
authors.initials: D
authors.lastname: Mizel
authors.forename: Yuning G
authors.initials: YG
authors.lastname: Huang
authors.forename: Josie P
authors.initials: JP
authors.lastname: Briggs
authors.forename: Jurgen
authors.initials: J
authors.lastname: Schnermann
mesh_terms: D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology; D001713:Biphenyl Compounds; D001794:Blood Pressure / Q000502:physiology; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000235:genetics* / Q000502:physiology*; D004039:Diet, Sodium-Restricted; D004232:Diuretics / Q000494:pharmacology; D004656:Enalapril / Q000494:pharmacology; D005665:Furosemide / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D007606:Juxtaglomerular Apparatus / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012313:RNA / Q000096:biosynthesis / Q000302:isolation & purification; D012083:Renin / Q000097:blood* / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013686:Telemetry; D013777:Tetrazoles / Q000494:pharmacology
chemical_list: D000318:Adrenergic beta-Agonists; D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D004232:Diuretics; D013777:Tetrazoles; D012313:RNA; D004656:Enalapril; D005665:Furosemide; D051546:Cyclooxygenase 2; D012083:Renin; D007545:Isoproterenol; C081643:candesartan