Mice lacking DARPP-32 did not exhibit ANP-induced natriuresis and had significantly increased mean arterial blood pressure compared to wild type mice, confirming its role in ANP signaling.
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.
EKLÖF et al. (Mon,) conducted a other in Blood pressure and sodium metabolism. DARPP-32 gene knockout and ANP administration vs. Wild type mice was evaluated on Natriuresis, renal Na+, K+-ATPase activity, and mean arterial blood pressure. Mice lacking DARPP-32 did not exhibit ANP-induced natriuresis and had significantly increased mean arterial blood pressure compared to wild type mice, confirming its role in ANP signaling.
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