Altered protein phosphatase 1 (PP1) activity and expression contribute to the differential regulation of proximal tubule NHE3 before and after onset of hypertension in SHR

TL;DRAbstract

We have previously demonstrated that NHE3 activity is higher in the proximal tubule of young pre‐hypertensive SHR (Y‐SHR) compared to adult hypertensive SHR (A‐SHR). This fall in NHE3 activity with blood pressure increase was associated with a higher ratio of phosphorylated NHE3 at serine 552 to total NHE3 (P‐NHE3/ total). The present study was undertaken to test the hypothesis that the increased levels of phosphorylated NHE3 at the PKA consensus site serine 552 was due to an increase of PKA activity, or a decrease of PP1 activity, or both. To confirm that PKA‐mediated phosphorylation of NHE3 regulation is altered in SHR, we examined the effect of 6MB‐cAMP (an cAMP analog that specifically activates PKA) on both phosphorylation levels and activity of NHE3 in young and adult SHR. We found that the 6MB‐cAMP‐induced increase in the levels of NHE3 phosphorylation at the serine 552 was much higher in the renal cortex from Y‐SHR than from A‐SHR (179 ± 14 vs. 36 ± 4%, P < 0.001). Likewise,

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