Heme oxygenase regulates renal arterial resistance and sodium excretion in cirrhotic rats.

Abstract

BACKGROUND & AIMS:

Heme oxygenase (HO) catabolizes heme into biliverdin, carbon monoxide (CO), and free iron. CO generated in endothelial and smooth muscle layers of blood vessels modulates vascular tone by inducing relaxation of vascular smooth muscle cells. The aim of this study was to verify the role played by HO in regulating renal arterial resistance and Na(+) excretion in cirrhosis.

METHODS:

Twenty control rats and 20 rats with CCl(4)(-) induced cirrhosis, 10 of which were chronically treated with the HO inducer cobalt-protoporphyrin (CoPP), were studied. Pressurized renal interlobar arteries were challenged with increasing doses of phenylephrine (PE) and acetylcholine (ACh). Dose-response curves were evaluated under basal conditions and after inhibition of HO with chromium-mesoporphyrin (CrMP). HO-1 (inducible form) and HO-2 (constitutive form) expression was measured in the main and interlobar renal arteries. Serum and urinary levels of Na(+) and creatinine were also evaluated.

RESULTS:

In renal interlobar arteries from cirrhotic rats, the response to PE was increased, while that to ACh was blunted. After HO inhibition, the responsiveness to these vasoactive substances was comparable in the two groups. In cirrhotic rats, HO-1 expression was impaired in the main and the interlobar renal arteries. Chronic HO induction normalized the response to the vasoconstrictor, but not to the vasodilator. Cirrhotic rats treated with CoPP showed higher urinary Na(+) concentration and fractional Na(+) excretion, compared to both untreated cirrhotic and control rats.

CONCLUSIONS:

In cirrhotic rats, an impaired HO-1 expression promotes vasoconstriction of renal interlobar arteries. Chronic HO induction normalizes the sensitivity to PE and promotes Na(+) excretion.

• Authors: Marco Di Pascoli, Francesca Zampieri, Santina Quarta, David Sacerdoti, Carlo Merkel, Angelo Gatta, Massimo Bolognesi
• Journal: Journal of hepatology (J Hepatol) Vol. 54 Issue 2 Pg. 258-64 (Feb 2011) ISSN: 1600-0641 [Electronic] Netherlands
• PMID: 21055838 (Publication Type: Journal Article)
• Copyright: Copyright © 2010 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Chemical References

• Mesoporphyrins
• chromium mesoporphyrin
• Phenylephrine
• Carbon Monoxide
• Sodium
• Heme Oxygenase (Decyclizing)
• Heme Oxygenase-1
• heme oxygenase-2
• Acetylcholine

Topics

• Acetylcholine (pharmacology)
• Animals
• Blotting, Western
• Carbon Monoxide (physiology)
• Heme Oxygenase (Decyclizing) (analysis, physiology)
• Heme Oxygenase-1 (analysis, physiology)
• Liver Cirrhosis, Experimental (enzymology, physiopathology)
• Male
• Mesoporphyrins (pharmacology)
• Phenylephrine (pharmacology)
• Rats
• Rats, Wistar
• Renal Artery (drug effects, physiology)
• Sodium (metabolism)
• Vascular Resistance