dinoprost and Renal-Artery-Obstruction

Hypertensive patients with renovascular disease (RVD) may be exposed to increased oxidative stress, possibly related to activation of the renin-angiotensin system.. We measured the urinary excretion of 8-iso-prostaglandin (PG) F2alpha and 11-dehydro-thromboxane (TX) B2 as indexes of in vivo lipid peroxidation and platelet activation, respectively, in 25 patients with RVD, 25 patients with essential hypertension, and 25 healthy subjects. Plasma renin activity in peripheral and renal veins, angiotensin II in renal veins, cholesterol, glucose, triglycerides, homocysteine, and antioxidant vitamins A, C, and E were also determined. Patients were also studied 6 months after a technically successful angioplasty of the stenotic renal arteries. Urinary 8-iso-PGF2alpha was significantly higher in patients with RVD (median, 305 pg/mg creatinine; range, 124 to 1224 pg/mg creatinine) than in patients with essential hypertension (median, 176 pg/mg creatinine; range, 48 to 384 pg/mg creatinine) or in healthy subjects (median, 123 pg/mg creatinine; range, 58 to 385 pg/mg creatinine). Urinary 11-dehydro-TXB2 was also significantly higher in RVD patients compared with healthy subjects. In RVD patients, urinary 8-iso-PGF2alpha correlated with 11-dehydro-TXB2 (r(s)=0.48; P<0.05) and renal vein renin (r(s)=0.67; P<0.005) and angiotensin II (r(s)=0.65; P=0.005) ratios. A reduction in 8-iso-PGF2alpha after angioplasty was observed in RVD patients with high baseline levels of lipid peroxidation. Changes in 8-iso-PGF2alpha were related to baseline lipid peroxidation (r(s)=-0.73; P<0.001), renal vein angiotensin II (r(s)=-0.70; P<0.01) and renin (r(s)=-0.63; P<0.05) ratios.. Lipid peroxidation is markedly enhanced in hypertensive patients with RVD and is related to activation of the renin-angiotensin system. Moreover, persistent platelet activation triggered or amplified by bioactive isoprostanes may contribute to the progression of cardiovascular and renal damage in this setting.

Topics: Adolescent; Adult; Aged; Angioplasty; Angiotensin II; Antioxidants; Biomarkers; Blood Glucose; Cholesterol; Cross-Sectional Studies; Dinoprost; F2-Isoprostanes; Female; Homocysteine; Humans; Hypertension; Hypertension, Renovascular; Lipid Peroxidation; Male; Middle Aged; Oxidative Stress; Platelet Activation; Reference Values; Renal Artery Obstruction; Renin; Renin-Angiotensin System; Thromboxane B2; Triglycerides; Vitamins

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.

Topics: Animals; Blood Pressure; Dinoprost; F2-Isoprostanes; Female; Free Radical Scavengers; Hypertension, Renovascular; Kidney Cortex; Oxidative Stress; Renal Artery Obstruction; Renal Circulation; Renin; Swine; Thiobarbituric Acid Reactive Substances

A total of 154 patients with essential hypertension (EH), 24 patients with renovascular hypertension (RVH), and 130 Wistar rats were investigated. PGE2 and PGF2 alpha levels were assayed radioimmunologically in renal venous blood and urine of the patients, and the synthesis of PGE2 and PGF2 alpha in renal tissue, renal PGE-9-ketoreductase activity and urinary PG excretion were measured in rats. It was demonstrated that the PGE2 synthesis was depressed in the vascular channel and the renal uropoietic system, with elevated F/E rations, in patients with arterial hypertension. Clinical and experimental studies showed prolonged and excessive salt consumption to be a cause of these changes, rooted in suppressed renal biosynthesis of both PGs and increased conversion of PGE2 to PGF2 alpha. In addition, renal PGE2 inactivation was increased in EH patients, as compared to those with RVH. PGE2 produced in the kidneys of EH patients is always a depressor natriuretic substance, whereas the role of PGF2 alpha is dependent on the water-salt balance. Furosemide and, to a smaller extent, other diuretics, as well as some hypotensive agents, increase urinary PG excretion and depress the F/E ratio in the urine. Repeated PGE2 infusions are shown to enhance the sensitivity of EH patients to hypotensive drugs, so they can be used for the treatment of refractory EH cases.

Topics: Adult; Animals; Blood Pressure; Dinoprost; Dinoprostone; Humans; Hypertension, Renovascular; Kidney; Male; Middle Aged; Muscle, Smooth, Vascular; Natriuresis; Prostaglandins E; Prostaglandins F; Rats; Rats, Inbred Strains; Renal Artery Obstruction; Sodium; Water-Electrolyte Balance