| First Author | Ramkumar N | Year | 2014 |
| Journal | Am J Physiol Renal Physiol | Volume | 307 |
| Issue | 8 | Pages | F931-8 |
| PubMed ID | 25122048 | Mgi Jnum | J:216183 |
| Mgi Id | MGI:5607839 | Doi | 10.1152/ajprenal.00367.2014 |
| Citation | Ramkumar N, et al. (2014) Collecting duct-specific knockout of renin attenuates angiotensin II-induced hypertension. Am J Physiol Renal Physiol 307(8):F931-8 |
| abstractText | The physiological and pathophysiological significance of collecting duct (CD)-derived renin, particularly as it relates to blood pressure (BP) regulation, is unknown. To address this question, we generated CD-specific renin knockout (KO) mice and examined BP and renal salt and water excretion. Mice containing loxP-flanked exon 1 of the renin gene were crossed with mice transgenic for aquaporin-2-Cre recombinase to achieve CD-specific renin KO. Compared with controls, CD renin KO mice had 70% lower medullary renin mRNA and 90% lower renin mRNA in microdissected cortical CD. Urinary renin levels were significantly lower in KO mice (45% of control levels) while plasma renin concentration was significantly higher in KO mice (63% higher than controls) during normal-Na intake. While no observable differences were noted in BP between the two groups with varying Na intake, infusion of angiotensin II at 400 ng.kg(-1).min(-1) resulted in an attenuated hypertensive response in the KO mice (mean arterial pressure 111 +/- 4 mmHg in KO vs. 128 +/- 3 mmHg in controls). Urinary renin excretion and epithelial Na(+) channel (ENaC) remained significantly lower in the KO mice following ANG II infusion compared with controls. Furthermore, membrane-associated ENaC protein levels were significantly lower in KO mice following ANG II infusion. These findings suggest that CD renin modulates BP in ANG II-infused hypertension and these effects are associated with changes in ENaC expression. |
