| First Author | Lorenz JN | Year | 2011 |
| Journal | Am J Physiol Renal Physiol | Volume | 301 |
| Issue | 3 | Pages | F615-21 |
| PubMed ID | 21632957 | Mgi Jnum | J:175251 |
| Mgi Id | MGI:5285031 | Doi | 10.1152/ajprenal.00158.2011 |
| Citation | Lorenz JN, et al. (2011) Renovascular hypertension using a modified two-kidney, one-clip approach in mice is not dependent on the {alpha}1 or {alpha}2 Na-K-ATPase ouabain-binding site. Am J Physiol Renal Physiol 301(3):F615-21 |
| abstractText | Endogenous cardiotonic steroids, through their interaction with the ouabain-binding site of the Na-K-ATPase alpha-subunit, have been implicated in a variety of cardiovascular disease states including hypertension. We have previously shown that ACTH-induced hypertension is abolished in mutant mice expressing ouabain-resistant alpha1- and alpha2-subunits. To further evaluate hypertension resistance in these mutant mice, we examined blood pressure changes in a modified model of 2-kidney, 1-clip (2K1C) renovascular hypertension. To reliably generate 2K1C hypertension, we used polyvinyl tubing (inner diameter: approximately 0.27 mm) to accurately gauge the degree of renal artery stenosis. Using this method, virtually all of the clipped mice became hypertensive and there was no incidence of apparent renal ischemia. By telemetry, in response to renal artery clipping, blood pressure in wild-type mice (alpha1 ouabain-resistant, alpha2 ouabain-sensitive) increased from 97 +/- 3 to 136 +/- 7 mmHg. In alpha1-resistant, alpha2-resistant mice, pressure increased from 93 +/- 2 to 123 +/- 4 mmHg, and in alpha1-sensitive, alpha2-resistant mice, blood pressure increased from 95 +/- 2 to 139 +/- 5 mmHg. Blood pressure changes were equivalent in all three groups. In sham mice, blood pressure did not change (96 +/- 1 to 95 +/- 2 mmHg). Renin mRNA expression was dramatically elevated in the left vs. the right kidney, and plasma renin concentration was elevated similarly in all genotypes. These data indicate that sensitivity of the alpha1- or alpha2-Na-K-ATPase binding site to cardiotonic steroids is not a prerequisite for the development of 2K1C renovascular hypertension. In addition, use of a polyurethane cuff to constrict the renal artery provides a reliable method for producing 2K1C hypertension in mice. |
