Two-Week Administration of Tempol Attenuates Both Hypertension and Renal Excretion of 8-Iso Prostaglandin F _2α

Abstract

8-Iso prostaglandin F2alpha (8-ISO) is formed nonenzymatically from the attack of superoxide radical on arachidonic acid. Therefore, 8-ISO is a marker of oxidative stress in vivo. We have recently shown that short-term administration of the membrane-permeable, metal-independent superoxide dismutase mimetic tempol (4-hydroxy-2, 2, 6, 6-tetramethyl piperidinoxyl) normalizes blood pressure in spontaneously hypertensive rats (SHR). The present study was designed to test whether prolonged administration of tempol ameliorates oxidative stress and hypertension in SHR. In control SHR (n=8), mean arterial pressure and heart rate were increased and renal blood flow and glomerular filtration rate were reduced compared with control Wistar-Kyoto rats (WKY) (n=7). Twenty-four-hour renal excretion of 8-ISO was significantly increased 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 rate 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, tempol 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-term administration of a superoxide scavenger reduces blood pressure and oxidative stress in vivo, this study suggests a role for oxygen radicals in the maintenance of hypertension in SHR.