Two-week administration of tempol attenuates both hypertension and renal excretion of 8-iso prostaglandin F-2 alpha

8-Iso prostaglandin F-2 alpha (8-ISO) is formed nonenzymatically from the a ttack of superoxide radical on arachidonic acid. Therefore, 8-ISO is a mark er of oxidative stress in vivo. We have recently shown that short-term admi nistration of the membrane-permeable, metal-independent superoxide dismutas e mimetic tempol (4-hydroxy-2, 2, 6, 6-tetramethyl piperidinoxyl) normalize s blood pressure in spontaneously hypertensive rats (SHR). The present stud y was designed to test whether prolonged administration of tempol ameliorat es oxidative stress and hypertension in SHR. In control SHR (n=8), mean art erial pressure and heart rate were increased and renal blood now and glomer ular filtration rate were reduced compared with control Wistar-Kyoto rats ( WKY) (n=7). Twenty-four-hour renal excretion of 8-ISO was significantly inc reased in SHR compared with WKY. Two weeks of tempol administration in the drinking water (1 mmol/L) to SHR (n=8) decreased mean arterial pressure by 18% (162+/-8 to 134+/-6 mm Hg, P<0.05), increased glomerular filtration rat e by 17% (1.6+/-0.2 to 1.9+/-0.3 mL/min), and decreased renal excretion of 8-ISO by 39% (9.8+/-0.7 to 6.0+/-0.7 ng/24 hours, P<0.05). In contrast, tem pol administration to WKY (n=6) had no significant effect on mean arterial pressure (115+/-5 versus 118+/-8 mm Hg), glomerular filtration rate (3.0+/- 0.4 versus 2.5+/-0.5 mL/min), or renal excretion of 8-ISO (7.9+/-0.4 versus 6.8+/-0.7 ng/24 hours). In conclusion, the SHR is a model of hypertension and renal vasoconstriction associated with oxidative stress. Because long-t erm administration of a superoxide scavenger reduces blood pressure and oxi dative stress in vivo, this study suggests a role for oxygen radicals in th e maintenance of hypertension in SHR.