Role of Vascular Extracellular Superoxide Dismutase in Hypertension

• Type of Material: Article
• Authors: Heinrich E. Lob, Emory University; Antony Vinh, Emory University; Li Li, Emory University; Yelena Blinder, Emory University; Stefan Offermanns, Max-Planck-Institute for Heart and Lung Research; David Harrison, Emory University
• Language: English
• Date: 2011-08-01
• Publisher: American Heart Association
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2011 American Heart Association, Inc.
• Final Published Version (URL): http://dx.doi.org/10.1161/HYPERTENSIONAHA.111.172718
• Title of Journal or Parent Work: Hypertension
• ISSN: 0194-911X
• Volume: 58
• Issue: 2
• Start Page: 232
• End Page: U213
• Grant/Funding Information: This work was supported by NIH R01 HL039006, P01 HL058000, P01 HL095070.; Drs. Lob and Vinh were supported by post-doctoral fellowships from the Amercian Heart Association.
• Keywords: BLOOD-PRESSURE; CENTRAL-NERVOUS-SYSTEM; OXIDATIVE STRESS; THIOL/DISULFIDE REDOX; Peripheral Vascular Disease; ANGIOTENSIN-II; Cardiovascular System & Cardiology; RELAXING FACTOR; NITRIC-OXIDE; II-INDUCED HYPERTENSION; inflammation; OBESE MICE; vasculature; central nervous system; blood pressure; Life Sciences & Biomedicine; Science & Technology; SMOOTH-MUSCLE; superoxide dismutase
• Research Categories: Health Sciences, Pharmacology; Health Sciences, Medicine and Surgery

Abstract

Previous studies indicate that superoxide is important in the modulation of blood pressure but have not specifically identified the cell types or organs involved. We created mice with loxP sites flanking the extracellular superoxide dismutase (SOD3) gene. These mice were crossed with mice expressing inducible Cre-recombinase driven by the smooth muscle myosin heavy chain promoter allowing tissue-specific deletion of SOD3. Deletion of SOD3 increased vascular superoxide and reduced vascular NO levels as detected by electron spin resonance. Despite these changes in NO and superoxide, we did not observe increases in vascular inflammation caused by angiotensin II. Moreover, deletion of vascular SOD3 did not augment hypertension in response to angiotensin II. In additional studies, we also deleted SOD3 from the circumventricular organs by intracerebroventricular injection of an adenovirus encoding Cre-recombinase. Although this raised blood pressure and augmented the hypertension caused by angiotensin II, these responses were not further increased by vascular deletion of SOD3. These data suggest that the extracellular superoxide dismutase in vascular smooth muscle is not involved in the genesis of angiotensin II-induced hypertension and further emphasize the role of central SOD3 in the modulation of blood pressure.