Increased oxidative stress in experimental renovascular hypertension.

Abstract

The pathophysiological mechanisms responsible for maintenance of chronic renovascular hypertension remain undefined. Excess angiotensin II generation may lead to release of reactive oxygen species and increased vasoconstrictor activity. To examine the potential involvement of oxidation-sensitive mechanisms in the pathophysiology of renovascular hypertension, blood samples were collected and renal blood flow measured with electron-beam computed tomography 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 pigs. Levels of prostaglandin F2alpha (PGF(2alpha))-isoprostanes, vasoconstrictors and markers of oxidative stress, also were significantly increased (157+/-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 still correlated directly with the increase in arterial pressure (r=0.7) but not with plasma renin activity. Stenotic kidney blood flow was decreased at both studies. In shock-frozen cortical tissue, ex vivo endogenous intracellular 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 is associated with increased systemic oxidative stress. When plasma renin activity later declines, PGF(2alpha)-isoprostanes remain elevated, possibly due to local activation or slow responses to angiotensin II, and may participate in sustenance of arterial pressure. Moreover, oxidation-sensitive mechanisms may influence ischemic and hypertensive parenchymal renal injury.

• Authors: L O Lerman, K A Nath, M Rodriguez-Porcel, J D Krier, R S Schwartz, C Napoli, J C Romero
• Journal: Hypertension (Dallas, Tex. : 1979) (Hypertension) Vol. 37 Issue 2 Pt 2 Pg. 541-6 (Feb 2001) ISSN: 1524-4563 [Electronic] United States
• PMID: 11230332 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• F2-Isoprostanes
• Free Radical Scavengers
• Thiobarbituric Acid Reactive Substances
• 8-epi-prostaglandin F2alpha
• Dinoprost
• Renin

Topics

• Animals
• Blood Pressure
• Dinoprost (analogs & derivatives, blood)
• F2-Isoprostanes
• Female
• Free Radical Scavengers (analysis)
• Hypertension, Renovascular (blood, etiology, physiopathology)
• Kidney Cortex (blood supply, metabolism)
• Oxidative Stress
• Renal Artery Obstruction (complications)
• Renal Circulation
• Renin (blood)
• Swine
• Thiobarbituric Acid Reactive Substances (analysis)