Faculty Collaboration Database

Expression and actions of heme oxygenase in the renal medulla of rats. Hypertension 2000 Jan;35(1 Pt 2):342-7

Date

01/21/2000

Pubmed ID

10642322

DOI

10.1161/01.hyp.35.1.342

Scopus ID

2-s2.0-0033979878 (requires institutional sign-in at Scopus site)   91 Citations

Abstract

Recent studies have shown that the heme oxygenase (HO) product, carbon monoxide (CO), induces vasodilation and that inhibition of HO produces a sustained hypertension in rats. Given the importance of renal medullary blood flow (MBF) in the long-term control of arterial blood pressure, we hypothesized that the HO/CO system may play an important role in maintaining the constancy of blood flow to the renal medulla, which in turn contributes to the antihypertensive effects of the renal medulla. To test this hypothesis, we first determined the expression of 2 isoforms of HO (HO-1 and HO-2) in the different kidney regions. By Northern blot analyses, the abundance of both isozyme mRNAs was found highest in the renal inner medulla and lowest in the renal cortex. The transcripts for HO-1 in the renal outer medulla and inner medulla were 2.5 and 3.7 times that expressed in the renal cortex and those for HO-2 in the outer medulla and inner medulla were 1.3 and 1.6 times that expressed in the renal cortex, respectively. Western blot analyses of both enzymes showed the same expression pattern in these kidney regions as the mRNAs. To determine the role that HO plays in the control of renal MBF, we examined the effect of the HO inhibitor zinc deuteroporphyrin 2,4-bis glycol (ZnDPBG) on cortical blood flow and MBF in anesthetized rats. ZnDPBG was given by renal medullary interstitial infusion, and cortical blood flow and MBF were measured by laser Doppler flowmetry. Renal medullary interstitial infusion of ZnDPBG at a dose of 60 nmol/kg per minute produced a 31% decrease in MBF over a period of 60 minutes as measured by laser Doppler flow signal (0.62+/-0.02 vs 0.43+/-0.04 V in control vs ZnDPBG). With the use of an in vivo microdialysis technique, ZnDPBG was found to significantly reduce renal medullary cGMP concentrations when infused into the renal medullary interstitial space. These results suggest that both HO-1 and HO-2 are highly expressed in the renal medulla, that HO and its products play an important role in maintaining the constancy of blood flow to the renal medulla, and that cGMP may mediate the vasodilator effect of HO products in the renal medullary circulation.

Author List

Zou AP, Billington H, Su N, 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
Blotting, Northern
Blotting, Western
Cyclic GMP
Fluorescent Dyes
Gene Expression Regulation, Enzymologic
Heme Oxygenase (Decyclizing)
Heme Oxygenase-1
Kidney Cortex
Kidney Medulla
Laser-Doppler Flowmetry
Male
Microdialysis
Oxygen
RNA, Messenger
Rats
Rats, Sprague-Dawley
Renal Circulation
Triglycerides
Ultrasonography
Zinc