Increased expression of Na,K-ATPase and a selective increase in phosphorylation at Ser-11 in the cortex of the 2-kidney, 1-clip hypertensive rat

• Published in: American journal of hypertension 2012-04, Vol.25 (4), p.487-491
• Main Authors: Kava, Lauren, Rossi, Noreen F., Mattingly, Raymond, Yingst, Douglas R.
• Format: Article
• Language: English
• Subjects: Actins; Amino Acid Sequence; Angiotensin II - blood; Angiotensin II - metabolism; Animals; Arterial hypertension. Arterial hypotension; Biological and medical sciences; Blood and lymphatic vessels; Blood Pressure - drug effects; Cardiology. Vascular system; Constriction, Pathologic; Experimental diseases; Hypertension, Renovascular - physiopathology; Kidney Cortex - metabolism; Kidney Tubules, Proximal - metabolism; Male; Medical sciences; Phosphorylation; Rats; Rats, Sprague-Dawley; Renal Artery - pathology; Serine - metabolism; Sodium-Potassium-Exchanging ATPase - biosynthesis
• ISSN: 0895-7061; 1941-7225; 1879-1905
• DOI: 10.1038/ajh.2011.247

Background The mechanism by which blood pressure increases during renovascular hypertension is incompletely understood. We, therefore, tested the hypothesis that in the 2-kidney, 1-clip (2K-1C) rat, in which hypertension develops due to increased angiotensin II (Ang II) levels, there is increased expression and phosphorylation of Na,K-ATPase at Ser-11 and Ser-18 in the kidney cortex. The rationale is Ang II is reported to directly stimulate Na,K-ATPase activity in proximal tubules, which reabsorb 2/3 of filtered sodium, via increased phosphorylation at Ser-11 and Ser-18 and the Na,K-ATPase drives sodium reabsorption. Methods Five-week-old Sprague-Dawley rats underwent unilateral or sham clipping of the right renal artery and placement of telemetry transmitters. Six weeks later blood pressure and plasma Ang II were measured and kidneys harvested. The amount of Na,K-ATPase, phosphorylation at Ser-11 and Ser-18, and the expression of β-actin in each kidney cortex were measured by quantitative immunoblotting. Results Clipping significantly increased mean arterial pressure from 110 ± 3 to 148 ± 13 mm Hg, plasma Ang II, cortical Na,K-ATPase in the unclipped kidney of 2K-1C compared to sham-clipped rats, the total cortical Na,K-ATPase in both kidneys compared to sham-clipped rats, and the extent to which the Na,K-ATPase was phosphorylated at Ser-11. Clipping did not significantly change phosphorylation at Ser-18, β-actin, or the total protein in the cortexes of both kidneys. Conclusions Thus, in the kidney cortex of rats with renovascular hypertension there is increased expression of Na,K-ATPase and a selective increase in its phosphorylation at Ser-11 that could increase the capacity to reabsorb sodium and water.