Increased oxidative stress in experimental renovascular hypertension

The pathophysiological mechanisms responsible for maintenance of chronic re novascular hypertension remain undefined, Excess angiotensin II generation may lead to release of reactive oxygen species and increased vasoconstricto r activity. To examine the potential involvement of oxidation-sensitive mec hanisms in the pathophysiology of renovascular hypertension, blood samples were collected and renal blood flow measured with electron-beam computed to mography in pigs 5 and 10 weeks after induction of unilateral renal artery stenosis (n=7) or sham operation (n=7). Five weeks after procedure, plasma renin activity and mean arterial pressure were elevated in hypertensive pig s. Levels of prostaglandin F2 alpha (PGF2 alpha)-isoprostanes, vasoconstric tors and markers of oxidative stress, also were significantly increased (15 7+/-21 versus 99+/-16 pg/mL; P<0.05) and correlated with both plasma renin activity (r=0.83) and arterial pressure (r=0.82). By 10 weeks, plasma renin activity returned to baseline but arterial pressure remained elevated (144 +/-10 versus 115+/-5 mm Hg; P<0.05). Isoprostane levels remained high and s till correlated directly with the increase in arterial pressure (r=0.7) but not with plasma renin activity. Stenotic kidney blood flow was decreased a t both studies. In shock-frozen cortical tissue, ex vivo endogenous intrace llular radical scavengers were significantly decreased in both kidneys. The present study demonstrates, for the first time, that in early renovascular hypertension, an increase in plasma renin activity and arterial pressure i s associated with increased systemic oxidative stress. When plasma renin ac tivity later declines, PGF(2 alpha)-isoprostanes remain elevated, possibly due to local activation or slow responses to angiotensin II, and may partic ipate in sustenance of arterial pressure, Moreover, oxidation-sensitive mec hanisms may influence ischemic and hypertensive parenchymal renal injury.