Faculty Collaboration Database

Increased renal medullary oxidative stress produces hypertension. Hypertension 2002 Feb;39(2 Pt 2):667-72

Date

03/08/2002

Pubmed ID

11882628

DOI

10.1161/hy0202.103469

Scopus ID

2-s2.0-0036181930 (requires institutional sign-in at Scopus site)   150 Citations

Abstract

The present study examined whether chronic increased oxidative stress within the medulla of the kidney lowers medullary blood flow and leads to hypertension. Optical fibers were implanted into the renal cortex and medulla of uninephrectomized Sprague-Dawley rats (Harlan Sprague-Dawley, Madison, Wis) for the daily measurement of blood flow to these regions using laser-Doppler flowmetry techniques, while arterial pressure was measured from an indwelling aortic catheter. A renal medullary interstitial catheter was implanted for the continuous delivery of the superoxide dismutase (SOD) inhibitor, diethyldithiocarbamic acid (DETC), at a dose of 7.5 mg/kg/d. Renal interstitial superoxide (O(2)(-)) levels were determined by perfusing an O(2)(-) sensitive fluorescent dye, dihydroethidium, through a microdialysis probe implanted into the medulla. Urine samples (24 hours) were collected for measurements of isoprostane excretion. The results indicate that medullary DETC infusions increased tissue O(2)(-) concentrations in the renal medulla (93.4 +/- 22.3,n=8, saline and 867.3 +/- 260.2, n=8, DETC; fluorescence units) and increased urinary 8-isoprostane excretion (4.1 +/- 0.4 ng/d, n=9, saline and 8.8 +/- 1.6 ng/d, n=10, DETC). Mean arterial pressure increased 24 hours after the start of intrarenal DETC infusion and remained nearly 20 mm Hg above control pressure throughout the 5 days of medullary SOD inhibition. During chronic medullary DETC infusion, medullary blood flow was significantly reduced (42.7%), whereas cortical blood flow was unchanged. Intravenous infusion of the same dose of DETC produced no changes in renal medullary or cortical blood flow or arterial blood pressure. The present experiments indicate that an increase in superoxide concentration within the renal medulla selectively reduces medullary blood flow resulting in chronic hypertension.

Author List

Makino A, Skelton MM, Zou AP, Roman RJ, 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
Blood Pressure
Ditiocarb
Hypertension
Isoprostanes
Kidney Medulla
Male
Oxidative Stress
Rats
Rats, Sprague-Dawley
Reactive Oxygen Species