Antihypertensive Response to Prolonged Tempol in the Spontaneously Hypertensive Rat

Kidney Int. 2005 Jul;68(1):179-87. doi: 10.1111/j.1523-1755.2005.00392.x.

Abstract

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 F(2alpha) (PGF(2alpha)) (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) [NO(2)+ NO(3) (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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antioxidants / pharmacology*
  • Blood Pressure / drug effects
  • Catecholamines / blood
  • Cyclic N-Oxides / pharmacology*
  • Dinoprost / analogs & derivatives
  • Dinoprost / metabolism
  • Endothelin-1 / blood
  • Hypertension / drug therapy*
  • Male
  • Oxidative Stress / drug effects
  • Rats
  • Rats, Inbred SHR
  • Renin / blood
  • Sodium Chloride / metabolism
  • Spin Labels

Substances

  • Antioxidants
  • Catecholamines
  • Cyclic N-Oxides
  • Endothelin-1
  • Spin Labels
  • 8-epi-prostaglandin F2alpha
  • Sodium Chloride
  • Dinoprost
  • Renin
  • tempol