HO-1 induction lowers blood pressure and superoxide production in the renal medulla of angiotensin II hypertensive mice

Department of Physiology and Biophysics, Center for Excellence in Cardiovascular-Renal Research, University of Mississippi Medical Center, Jackson, Mississippi Submitted 24 August 2006 ; accepted in final form 21 December 2006 Heme oxygenase-1 (HO-1) induction can attenuate the development of angiot...

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Published in:American journal of physiology. Regulatory, integrative and comparative physiology integrative and comparative physiology, 2007-04, Vol.292 (4), p.R1472-R1478
Main Authors: Vera, Trinity, Kelsen, Silvia, Yanes, Licy L, Reckelhoff, Jane F, Stec, David E
Format: Article
Language:English
Subjects:
ACE inhibitors
Angiotensin II - administration & dosage
Angiotensin II - pharmacology
Animals
Blood Pressure - physiology
Enzyme Induction
Heme Oxygenase-1 - biosynthesis
Heme Oxygenase-1 - genetics
Hypertension
Hypertension, Renal - chemically induced
Hypertension, Renal - metabolism
Hypertension, Renal - physiopathology
Implants, Experimental
Infusions, Intravenous
Injections, Subcutaneous
Kidney Medulla - enzymology
Kidney Medulla - metabolism
Kidneys
Male
Mice
Mice, Inbred C57BL
Oxygen
Protoporphyrins - administration & dosage
Protoporphyrins - pharmacology
Rodents
Studies
Superoxides - metabolism
Vasoconstrictor Agents - administration & dosage
Vasoconstrictor Agents - pharmacology
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Summary:Department of Physiology and Biophysics, Center for Excellence in Cardiovascular-Renal Research, University of Mississippi Medical Center, Jackson, Mississippi Submitted 24 August 2006 ; accepted in final form 21 December 2006 Heme oxygenase-1 (HO-1) induction can attenuate the development of angiotensin II (ANG II)-dependent hypertension. However, the mechanism by which HO-1 lowers blood pressure in this model is not clear. The goal of this study was to test the hypothesis that induction of HO-1 in the kidney can attenuate the increase in reactive oxygen species (ROS) generation in the kidney that occurs during ANG II-dependent hypertension. Mice were divided into four groups, control (Con), cobalt protoporphyrin (CoPP), ANG II, and ANG II + CoPP. CoPP treatment (50 mg/kg) was administered in a single subcutaneous injection 2 days prior to implantation of an osmotic minipump that infused ANG II at a rate of 1 µg·kg –1 ·min –1 . At the end of this period, mean arterial blood pressure (MAP) averaged 93 ± 5, 90 ± 5, 146 ± 8, and 105 ± 6 mmHg in Con, CoPP-, ANG II-, and ANG II + CoPP-treated mice. To determine whether HO-1 induction resulted in a decrease in ANG II-stimulated ROS generation in the renal medulla, superoxide production was measured. Medullary superoxide production was increased by ANG II infusion and normalized in mice pretreated with CoPP. The reduction in ANG II-mediated superoxide production in the medulla with CoPP was associated with a decrease in extracellular superoxide dismutase protein but an increase in catalase protein and activity. These results suggest that reduction in superoxide and possibly hydrogen peroxide production in the renal medulla may be a potential mechanism by which induction of HO-1 with CoPP lowers blood pressure in ANG-II dependent hypertension. kidney; reactive oxygen species; cobalt protoporphyrin Address for reprint requests and other correspondence: D. E. Stec, Assistant Professor, Dept. of Physiology & Biophysics, Univ. of Mississippi Medical Center, 2500 North State St., Jackson, MS 39216-4505 (e-mail: dstec{at}physiology.umsmed.edu )
ISSN:0363-6119
1522-1490
DOI:10.1152/ajpregu.00601.2006