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(Circulation. 2000;101:1722.)
© 2000 American Heart Association, Inc.
Basic Science Reports |
Vascular Superoxide Production and Vasomotor Function in Hypertension Induced by Deoxycorticosterone Acetate–Salt
From the Division of Cardiology, Emory University School of Medicine and Atlanta VA Hospital, Atlanta, Ga.
Correspondence to David G. Harrison, MD, 319 WMRB, 1639 Pierce Dr, Atlanta, GA 30322. E-mail dharr02{at}emory.edu
Background—Angiotensin II–induced hypertension is associated with increased vascular superoxide production, which contributes to hypertension caused by the octapeptide. In cell culture, stretch increases endothelial and vascular smooth muscle production of reactive oxygen species (ROS). In perfused isolated vessels, elevations of pressure can increase vessel angiotensin II production. The effects of low-renin hypertension on vascular ROS production remain unclear. Furthermore, the role of ROS in vascular function and hypertension in low-renin hypertension is undefined.
Methods and Results—Rats were treated with DOCA and saline drinking water for 3 weeks. Both systolic blood pressure (189±4 versus 126±2 mm Hg) and aortic superoxide production (3972±257 versus 852±287, P<0.05) were increased compared with controls. Relaxations of vascular segments to acetylcholine (ACh, 100±2% versus 75±2%, P<0.05) and the calcium ionophore A23187 (92±2% versus 72±3%, P<0.05) were also impaired in DOCA-salt. Heparin-binding superoxide dismutase (1200 U/d IV for 3 days) had no effect on blood pressure but significantly improved relaxations to ACh and A23187. Losartan (25 mg · kg-1 · d-1 PO) for 7 days did not correct the hypertension or endothelium-dependent vessel relaxation in DOCA-salt rats, excluding a role of a local renin/angiotensin II system.
Conclusions—These findings indicate that increased vascular superoxide production occurs not only in angiotensin II–induced hypertension but also in hypertension known to be associated with low-renin states. Increased superoxide production alters large-vessel endothelium-dependent vascular relaxation but does not modulate blood pressure in low-renin hypertension.
Key Words: hypertension • angiotensin • free radicals • endothelium
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