| First Author | Eklöf AC | Year | 2001 |
| Journal | Clin Exp Hypertens | Volume | 23 |
| Issue | 6 | Pages | 449-60 |
| PubMed ID | 11478427 | Mgi Jnum | J:103307 |
| Mgi Id | MGI:3609106 | Doi | 10.1081/ceh-100104236 |
| Citation | Eklof AC, et al. (2001) Increased blood pressure and loss of anp-induced natriuresis in mice lacking DARPP-32 gene. Clin Exp Hypertens 23(6):449-60 |
| abstractText | Atrial natriuretic peptide (ANP) is an important regulator of sodium metabolism and indirectly of blood pressure. Evidence has accumulated that ANP regulates sodium metabolism through a cascade of steps involving an increase in the level of cGMP, activation of cGMP-dependent protein kinase (PKG), and inhibition of renal tubular Na+, K+-ATPase activity. One of the major substrates for PKG is DARPP-32. In the present study we observed that ANP does not induce natriuresis in mice that lack DARPP-32. In contrast, there was a 4-fold increase in urinary sodium excretion following ANP administration to wild type mice. ANP as well as Zaprinast, a selective inhibitor of cGMP phosophodiesterase, inhibited renal Na+, K+-ATPase activity in wild type mice but had no such effect in mice lacking DARPP-32. Mean arterial blood pressure, measured in conscious animals, was significantly increased in DARPP-32 deficient mice as compared to wild type mice. The results confirm that DARPP-32 acts as a third messenger in the ANP signaling pathway in renal tissue and suggest an important role of DARPP-32 in the maintenance of normal blood pressure. |
