title: Progression of glomerular filtration rate reduction determined in conscious Dahl salt-sensitive hypertensive rats.
abstract: Sequential changes in glomerular filtration rate during development of hypertension in the conscious Dahl salt-sensitive rats were determined using a new method for measurement. Using a miniaturized device, disappearance curves of fluorescein isothiocyanate-sinistrin were measured by transcutaneous excitation and real-time detection of the emitted light through the skin. Rats with implanted femoral venous catheters (dye injection and sampling) and carotid catheters (mean arterial pressure by telemetry) were studied, while maintained on a 0.4% NaCl diet and on days 2, 5, 7, 14, and 21 after switching to 4.0% (high-salt [HS]) diet. A separate group of rats were maintained on 0.4% for 21 days as a time control. Mean arterial pressure rose progressively from the last day of 0.4% (130±2 mm Hg) reaching significance by day 5 of HS and averaged 162±7 mm Hg by day 21. Urine albumin excretion was significantly elevated (×3) by day 7 of HS in Dahl salt-sensitive rats. Glomerular filtration rate reduced on day 14 of HS falling from 1.53±0.06 mL/min per 100 g body weight to 1.27±0.04. By day 21, glomerular filtration rate had fallen 28% to 1.1±0.04 mL/min per 100 g (t(1/2) 28.4±1.1 minute.) No significant reductions of creatinine clearance were observed throughout the study in response to HS demonstrating the insensitivity of creatinine clearance measurements even with creatinine measured using mass spectrometry. We conclude that the observed reduction of glomerular filtration rate was a consequence and not a cause of the hypertension and that this noninvasive approach could be used in these conscious Dahl salt-sensitive rats for a longitudinal assessment of renal function.
authors: Department of Physiology, Medical College of Wisconsin, Milwaukee, WI 53226, USA. cowley@mcw.edu
authors: Allen W
authors: AW
authors: Cowley
authors: Robert P
authors: RP
authors: Ryan
authors: Terry
authors: T
authors: Kurth
authors: Meredith M
authors: MM
authors: Skelton
authors: Daniel
authors: D
authors: Schock-Kusch
authors: Norbert
authors: N
authors: Gretz
mesh_terms: D000818:Animals; D001794:Blood Pressure; D003243:Consciousness; D003404:Creatinine / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D005919:Glomerular Filtration Rate / Q000502:physiology*; D006973:Hypertension / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D007668:Kidney / Q000503:physiopathology*; D008297:Male; D013058:Mass Spectrometry; D051381:Rats; D020303:Rats, Inbred Dahl; D012079:Renal Circulation
chemical_list: D003404:Creatinine
keywords: Dahl SS rat; GFR; creatinine clearance; salt-sensitive hypertension
references: Kidney Int Suppl. 1996 Jun;55:S9-13
references: 8743503
references: Hypertension. 1979 May-Jun;1(3):316-23
references: 551079
references: Am J Physiol. 1991 Sep;261(3 Pt 2):R595-602
references: 1887948
references: Am J Physiol Renal Physiol. 2012 Sep;303(5):F783-8
references: 22696603
references: J Am Soc Nephrol. 2011 Jul;22(7):1353-64
references: 21719791
references: Am J Kidney Dis. 2000 Dec;36(6 Suppl 3):S4-12
references: 11118153
references: Hypertension. 1997 Oct;30(4):975-83
references: 9336403
references: Exp Physiol. 2008 Aug;93(8):945-53
references: 18403445
references: Kidney Int. 2007 Jan;71(1):74-8
references: 17082757
references: Ann Clin Biochem. 2000 Jan;37 ( Pt 1):60-6
references: 10672374
references: Ann Intern Med. 2009 May 5;150(9):604-12
references: 19414839
references: Clin Pharmacokinet. 2003;42(14):1193-211
references: 14606929
references: Hypertension. 2013 Jan;61(1):18-26
references: 23172928
references: Physiol Res. 2012;61(Suppl 1):S35-S87
references: 22827876
references: Physiol Rev. 1992 Jan;72(1):231-300
references: 1731371
references: Clin Chem. 1992 Mar;38(3):403-7
references: 1547559
references: Eur J Clin Pharmacol. 1999 May;55(3):205-11
references: 10379636
references: Nephrol Dial Transplant. 1994;9(9):1222-4
references: 7816278
references: Nephrol Dial Transplant. 2009 Oct;24(10):2997-3001
references: 19461009
references: Naunyn Schmiedebergs Arch Pharmacol. 2006 Jun;373(3):204-11
references: 16736157
references: Cell Metab. 2012 Feb 8;15(2):201-8
references: 22326221
references: Curr Protoc Hum Genet. 2007 Jul;Chapter 17:Unit 17.3
references: 18428409
references: Kidney Int. 2010 Mar;77(6):519-26
references: 20032962
references: Ann N Y Acad Sci. 2001 Jun;940:395-406
references: 11458695
references: Gerontology. 2002 May-Jun;48(3):140-6
references: 11961366
references: J Am Soc Nephrol. 2008 Aug;19(8):1472-82
references: 18417720
references: Curr Hypertens Rep. 2012 Aug;14(4):345-9
references: 22569647
references: J Hypertens. 2000 Oct;18(10):1497-505
references: 11057439
references: Kidney Int. 2011 Jun;79(11):1254-8
references: 21368744
references: Am J Vet Res. 2007 Aug;68(8):807-11
references: 17669018
references: Am J Kidney Dis. 2012 Jan;59(1 Suppl 1):A7, e1-420
references: 22177944
references: Am J Physiol. 1986 Jul;251(1 Pt 2):F57-65
references: 3728685
references: Hypertension. 2001 Feb;37(2 Pt 2):456-61
references: 11230318
references: Am J Clin Nutr. 1972 Feb;25(2):231-44
references: 5009786
references: Eur J Med Chem. 2005 Oct;40(10):1056-61
references: 15919135
references: Contrib Nephrol. 1990;81:220-8
references: 2093501