| First Author | Stec DE | Year | 2012 |
| Journal | J Am Soc Nephrol | Volume | 23 |
| Issue | 5 | Pages | 834-41 |
| PubMed ID | 22323644 | Mgi Jnum | J:190012 |
| Mgi Id | MGI:5447641 | Doi | 10.1681/ASN.2011050455 |
| Citation | Stec DE, et al. (2012) Expression of heme oxygenase-1 in thick ascending loop of henle attenuates angiotensin II-dependent hypertension. J Am Soc Nephrol 23(5):834-41 |
| abstractText | Kidney-specific induction of heme oxygenase-1 (HO-1) attenuates the development of angiotensin II (Ang II) -dependent hypertension, but the relative contribution of vascular versus tubular induction of HO-1 is unknown. To determine the specific contribution of thick ascending loop of Henle (TALH) -derived HO-1, we generated a transgenic mouse in which the uromodulin promoter controlled expression of human HO-1. Quantitative RT-PCR and confocal microscopy confirmed successful localization of the HO-1 transgene to TALH tubule segments. Medullary HO activity, but not cortical HO activity, was significantly higher in transgenic mice than control mice. Enhanced TALH HO-1 attenuated the hypertension induced by Ang II delivered by an osmotic minipump for 10 days (139 +/- 3 versus 153 +/-2 mmHg in the transgenic and control mice, respectively; P<0.05). The lower blood pressure in transgenic mice associated with a 60% decrease in medullary NKCC2 transporter expression determined by Western blot. Transgenic mice also exhibited a 36% decrease in ouabain-sensitive sodium reabsorption and a significantly attenuated response to furosemide in isolated TALH segments. In summary, these results show that increased levels of HO-1 in the TALH can lower blood pressure by a mechanism that may include alterations in NKCC2-dependent sodium reabsorption. |
