Vascular Biology – Hemodynamics – Hypertension
Kidney International (2005) 68, 179–187; doi:10.1111/j.1523-1755.2005.00392.x
Antihypertensive response to prolonged tempol in the spontaneously hypertensive rat
WILLIAM J WELCH, MARGARIDA MENDONCA, JONATHAN BLAU, ALEX KARBER, KATHRYN DENNEHY, KINJAL PATEL, YUEN-SUM LAO, PEDRO A JOSÉ and CHRISTOPHER S WILCOX
School of Pharmacy, University of Missouri, Kansas City, Missouri; Division of Nephrology and Hypertension, Department of Medicine, Georgetown University Medical Center, Washington, DC; and Department of Pediatrics, Georgetown University Medical Center, Washington, DC
Correspondence: Christopher S. Wilcox, M.D., Ph.D., George E. Schreiner Professor of Medicine, Chief, Division of Nephrology and Hypertension, Georgetown University Medical Center, PHC F6003, 3800 Reservoir Road, NW, Washington, DC 20007. E-mail: wilcoxch@georgetown.edu
Received 6 September 2004; Revised 20 December 2004; Re-revised 13 January 2005; Accepted 28 January 2005.
Abstract
Antihypertensive response to prolonged tempol in the spontaneously hypertensive rat.
Introduction
Tempol is a permeant nitroxide superoxide dismutase (SOD) mimetic that lowers mean arterial pressure (MAP) in spontaneously hypertensive rats (SHRs). We investigated the hypothesis that the antihypertensive response entails a negative salt balance, blunting of plasma renin activity (PRA), endothelin-1 (ET-1), or catecholamines or correction of oxidative stress as indexed by 8-isoprostane prostaglandin F2
(PGF2) (8-Iso).
Methods
Groups (N = 6 to 8) of SHRs were infused for 2 weeks with vehicle or tempol (200 nmol/kg/min) or given tempol (2 mmol/L) in drinking water.
Results
Tempol infusion reduced the MAP of anesthetized SHRs (150 
5 vs. 126 6 mm Hg) (P < 0.005). Oral tempol did not change the heart rate but reduced the MAP of conscious SHRs (-23 6 mm Hg) (P < 0.01) but not Wistar-Kyoto (WKY) rats. Tempol infusion increased the PRA (2.2 0.2 vs. 5.0 0.9 ng/mL/hour) (P < 0.005), did not change excretion of nitric oxide (NO) [NO2 + NO3 (NOx)], ET-1, or catecholamines but reduced excretion of 8-Iso (13.2 1.4 vs. 9.6 0.9 ng/24 hours; P < 0.01). Cumulative Na+ balance and gain in body weight were unaltered by tempol infusion. Tempol prevented a rise in MAP with high salt intake.
Conclusion
Tempol corrects hypertension without a compensatory sympathoadrenal activation or salt retention. The response is independent of nitric oxide, endothelin, or catecholamines and occurs despite increased PRA. It is accompanied by a reduction in oxidative stress and is maintained during increased salt intake.
Keywords:
reactive oxygen species, isoprostane, salt balance, plasma renin activity, endothelin, catecholamines, hypertension
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