| First Author | Zhang J | Year | 2014 |
| Journal | Am J Physiol Renal Physiol | Volume | 306 |
| Issue | 3 | Pages | F344-50 |
| PubMed ID | 24285500 | Mgi Jnum | J:206146 |
| Mgi Id | MGI:5548009 | Doi | 10.1152/ajprenal.00515.2013 |
| Citation | Zhang J, et al. (2014) Enhanced expression and activity of Nox2 and Nox4 in the macula densa in ANG II-induced hypertensive mice. Am J Physiol Renal Physiol 306(3):F344-50 |
| abstractText | NAD(P)H oxidase (Nox)2 and Nox4 are the isoforms of Nox expressed in the macula densa (MD). MD-derived superoxide (O2(-)), primarily generated by Nox2, is enhanced by acute ANG II stimulation. However, the effects of chronic elevations in ANG II during ANG II-induced hypertension on MD-derived O2(-) are unknown. We infused a slow pressor dose of ANG II (600 ng.min(-1).kg(-1)) for 2 wk in C57BL/6 mice and found that mean arterial pressure was elevated by 22.3 +/- 3.4 mmHg (P < 0.01). We measured O2(-) generation in isolated and perfused MDs and found that O2(-) generation by the MD was increased from 9.4 +/- 0.9 U/min in control mice to 34.7 +/- 1.8 U/min in ANG II-induced hypertensive mice (P < 0.01). We stimulated MMDD1 cells, a MD-like cell line, with ANG II and found that O2(-) generation increased from 921 +/- 91 to 3,687 +/- 183 U.min(-1).10(5) cells(-1), which was inhibited with apocynin, oxypurinol, or NS-398 by 46%, 14%, and 12%, respectively. We isolated MD cells using laser capture microdissection and measured mRNA levels of Nox. Nox2 and Nox4 levels increased by 3.7 +/- 0.17- and 2.6 +/- 0.15-fold in ANG II-infused mice compared with control mice. In MMDD1 cells treated with Nox2 or Nox4 small interfering (si)RNAs, ANG II-stimulated O2(-) generation was blunted by 50% and 41%, respectively. In cells treated with p22(phox) siRNA, ANG II-stimulated O2(-) generation was completely blocked. In conclusion, we found that a subpressor dose of ANG II enhances O2(-) generation in the MD and that the sources of this O2(-) are primarily Nox2 and Nox4. |
