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001-es BibID:	BIBFORM061612
Első szerző:	Stec, David E.
Cím:	Thick Ascending Loop of Henle (talh) Specific Expression of Ho-1 Attenuates the Development of Ang II-Dependent Hypertension / David E. Stec, Eva Csongradi, Trinity Vera, Heather A. Drummond, Nader G. Abraham
Dátum:	2010
ISSN:	0194-911X
Megjegyzések:	Recent studies have demonstrated an important antihypertensive action of renal heme oxygenase-1 (HO-1) induction; however, the specific contribution of thick ascending loop of Henle (TALH) derived HO-1 to this response is unknown. We generated a transgenic mouse model in which expression of the human HO-1 cDNA was controlled by the uromodulin (Tamm-Horsfall protein, THP) promoter (TALH-HHO1). Expression of the HO-1 transgene was only detected in isolated microdissected TALH tubule segments by rt-PCR. TALH-HHO1 mice exhibited a significant increase in medullary HO-1 protein which co-localized with endogenous THP protein as determined by confocal microscopy. HO activity was significantly increased in the medulla of TALH-HHO1 mice as compared to controls (25?7 vs. 151 30 pmoles/bilirubin/ mg/hr, n=6, p0.05), however, no difference in cortical HO activity was observed between TALH-HHO1 and non-transgenic mice. The effect of enhanced TALH HO-1 on the blood pressure response to increased Angiotensin II (Ang II) was determined in mice in which Ang II (1 g/min/kg. s.c.) was infused via an osmotic minipump for 10 days. Conscious blood pressures were measured over the last five days using implanted catheters. Ang II hypertension was significantly attenuated in TALH-HHO1 mice as compared to non-transgenic mice and averaged 139?3 vs. 153?2 mmHg (n=5, p0.05) in each group respectively. The decrease in blood pressure in TALH-HHO1 transgenic mice was associated with a 60% decrease in the level of the NKCC2 transporter in the medulla as determined by Western blot. TALH-HHO1 mice also exhibited a 36% decrease in sodium reabsorption measure in isolated TAHL tubule segments by ouabain sensitive rubidium (Rb) uptake. Our results demonstrate that increased levels of HO-1 in the TALH can lower blood pressure via a mechanism that may include alterations in NKCC2 dependent sodium reabsorption.
Tárgyszavak:	Orvostudományok Egészségtudományok idézhető absztrakt
Megjelenés:	Hypertension 56 : 5 (2010), p. e60. -
További szerzők:	Csongrádi Éva (1969-) (szakorvos) Vera, Trinity Drummond, Heather A. Abraham, Nader G. (tudományos segédmunkatárs)
Internet cím:	Intézményi repozitóriumban (DEA) tárolt változat
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