Abstract 519: Increased Renal Angiotensinogen Expression in Non-clipped Kidneys of 2-Kidney 1-Clip Hypertensive Rats

In 2-kidney 1-clip (2K1C) hypertension, intrarenal angiotensin II (Ang II) levels are increased in both kidneys but the mechanisms for augmentation of Ang II may be different. We recently reported that urinary angiotensinogen (AGT) is increased only in the non-clipped kidneys. However, it has not been determined if these changes are accompanied by augmentation of intrarenal AGT mRNA synthesis in the non-clipped kidneys of 2K1C hypertensive rats. Experiments were performed on male Sprague-Dawley rats (n=11) subjected to left renal arterial clipping (.25 mm gap) and followed for 18-21 days prior to anesthesia and separate measurements of renal function. Systolic arterial pressure increased to 180±3 mmHg compared to 126±4 mmHg in sham operated rats. There were no significant differences in water intake, body weights, and 24 hour urine volume and sodium excretion in awake rats. Separate measurements of renal function showed that renal plasma flow and glomerular filtration rate were similar in clipped and non-clipped kidneys and not different from those in sham rats. However, urine flow, sodium excretion and urinary AGT (uAGT) excretion were significantly greater in non-clipped kidneys compared to clipped and sham kidneys. While kidney AGT protein levels were not increased significantly, AGT transcript measured by real time RT-PCR revealed that the AGT mRNA levels in the cortex were 2.15 fold significantly greater in the non-clipped kidneys than in sham (1.0±.1) or clipped kidneys (.98±.15). The results support the hypothesis that in the non-clipped kidneys of 2K1C rats there is an augmentation of intrarenal AGT mRNA synthesis which explains increased uAGT excretion rates and intrarenal Ang II levels.