Faculty Collaboration Database

Increased renal medullary H2O2 leads to hypertension. Hypertension 2003 Jul;42(1):25-30

Date

06/05/2003

Pubmed ID

12782642

DOI

10.1161/01.HYP.0000074903.96928.91

Scopus ID

2-s2.0-0038480710 (requires institutional sign-in at Scopus site)   124 Citations

Abstract

We have recently reported that exaggerated oxidative stress in the renal medulla due to superoxide dismutase inhibition resulted in a reduction of renal medullary blood flow and sustained hypertension. The present study tested the hypothesis that selective scavenging of O2*- in the renal medulla would prevent hypertension associated with this exaggerated oxidative stress. An indwelling, aortic catheter was implanted in nonnephrectomized Sprague-Dawley rats for daily measurement of arterial blood pressure, and a renal medullary interstitial catheter was implanted for continuous delivery of the superoxide dismutase inhibitor diethyldithiocarbamic acid (DETC, 7.5 mg x kg(-1) x d(-1)) and a chemical superoxide dismutase mimetic, 4-hydroxytetramethyl piperidine-1-oxyl (TEMPOL, 10 mg. kg-1. d-1). Renal medullary interstitial infusion of TEMPOL completely blocked DETC-induced accumulation of O2*- in the renal medulla, as measured by the conversion rate of dihydroethidium to ethidium in the dialysate and by urinary excretion of 8-isoprostanes. However, TEMPOL infusion failed to prevent DETC-induced hypertension, unless catalase (5 mg x kg(-1) d(-1)) was coinfused. Direct infusion of H2O2 into the renal medulla resulted in increases of mean arterial pressure from 115+/-2.5 to 131+/-2.1 mm Hg, which was similar to that observed in rats receiving the medullary infusion of both TEMPOL and DETC. The results indicate that sufficient catalase activity in the renal medulla is a prerequisite for the antihypertensive action of TEMPOL and that accumulated H2O2 in the renal medulla associated with exaggerated oxidative stress might have a hypertensive consequence.

Author List

Makino A, Skelton MM, Zou AP, Cowley AW Jr

Author

Allen W. Cowley Jr PhD Professor in the Physiology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Antihypertensive Agents
Antioxidants
Blood Pressure
Catalase
Catheters, Indwelling
Cyclic N-Oxides
Dinoprost
Ditiocarb
Enzyme Inhibitors
F2-Isoprostanes
Free Radical Scavengers
Hydrogen Peroxide
Hypertension
Kidney Medulla
Male
Oxidative Stress
Rats
Rats, Sprague-Dawley
Spin Labels
Superoxide Dismutase
Superoxides
Vasoconstriction