| First Author | Stockand JD | Year | 2010 |
| Journal | J Am Soc Nephrol | Volume | 21 |
| Issue | 11 | Pages | 1903-11 |
| PubMed ID | 20813869 | Mgi Jnum | J:185905 |
| Mgi Id | MGI:5430480 | Doi | 10.1681/ASN.2010040377 |
| Citation | Stockand JD, et al. (2010) Purinergic inhibition of ENaC produces aldosterone escape. J Am Soc Nephrol 21(11):1903-11 |
| abstractText | The mechanisms underlying "aldosterone escape," which refers to the excretion of sodium (Na(+)) during high Na(+) intake despite inappropriately increased levels of mineralocorticoids, are incompletely understood. Because local purinergic tone in the aldosterone-sensitive distal nephron downregulates epithelial Na(+) channel (ENaC) activity, we tested whether this mechanism mediates aldosterone escape. Here, urinary ATP concentration increased with dietary Na(+) intake in mice. Physiologic concentrations of ATP decreased ENaC activity in a dosage-dependent manner. P2Y(2)(-/-) mice, which lack the purinergic receptor, had significantly less increased Na(+) excretion than wild-type mice in response to high-Na(+) intake. Exogenous deoxycorticosterone acetate and deletion of the P2Y(2) receptor each modestly increased the resistance of ENaC to changes in Na(+) intake; together, they markedly increased resistance. Under the latter condition, ENaC could not respond to changes in Na(+) intake. In contrast, as a result of aldosterone escape, wild-type mice had increased Na(+) excretion in response to high-Na(+) intake regardless of the presence of high deoxycorticosterone acetate. These data suggest that control of ENaC by purinergic signaling is necessary for aldosterone escape. |
