(Hypertension. 1999;33:424-428.)
© 1999 American Heart Association, Inc.
Scientific Contributions |
Two-Week Administration of Tempol Attenuates Both Hypertension and Renal Excretion of 8-Iso Prostaglandin F2
From the Division of Nephrology and Hypertension, Georgetown University Medical Center, Washington, DC.
Correspondence to Christine G. Schnackenberg, PhD, Georgetown University Medical Center, Division of Nephrology and Hypertension, Bldg D, Room 385, 4000 Reservoir Rd NW, Washington, DC 20007.
Abstract—8-Iso
prostaglandin F2
(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.
Key Words: oxidative stress • isoprostanes • oxygen radicals • superoxide dismutase
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