Lack of PKCα leads to Altered Urea Transporter UT‐A1 and Aquaporin‐2 in Angiotensin II‐induced Hypertension

Regulation of urea transport in the renal inner medullary collecting duct (IMCD) is essential for urine concentration. Perfusing IMCD with hypertonic solutions stimulates protein kinase C (PKC) to increase urea permeability. Since angiotensin II (Ang II) activates PKC in many cell types, we tested the hypothesis that Ang II‐induced regulation of UT‐A1 is mediated by PKC. Osmotic minipumps delivered 400 ng/kg/min of Ang II to wild type or PKCα −/− mice for 7 days. Inner medullas were harvested and protein abundance was determined by immunoblot. Compared to untreated controls, Ang II had no effect on urine output of wild type mice (0.48 ± 0.15 vs 0.65 ± 0.10 ml/d), but increased that of PKCα −/− mice (1.0 ± 0.11 vs 2.0 ± 0.33, p<0.05). Systolic blood pressure increased in both groups (wild type: 103 ± 5 to 147 ± 15, PKCα −/− : 114 ± 4 to 147 ± 1 mm Hg, p<0.05). Ang II tended to increase UT‐A1 abundance in wild types (p<0.06) by not in PKCα −/− mice, suggesting a role for PKCα in Ang II‐induced increases in UT‐A1. Protein kinase A phosphorylates UT‐A1 at serines 486 and 499. S486 phosphorylation was unaltered in either group. AQP2 abundance was unchanged in Ang II‐treated wild types, but decreased in PKCα −/− mice (p<0.01) with Ang II treatment. We conclude that Ang II‐induced increases in UT‐A1 are mediated, in part, by PKCα and that PKCα protects against Ang II‐induced decreases in AQP2. Support: NIDDK.