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April 11, 2000Circulation280 citations

Vascular Superoxide Production and Vasomotor Function in Hypertension Induced by Deoxycorticosterone Acetate–Salt

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MSMark J. SomersEmory UniversityKMKreton MavromatisInterventional / Structural CardiologyZGZorina S. GalisVascular Medicine

Key Result

DOCA-salt induced low-renin hypertension in rats significantly increased aortic superoxide production (3972 vs 852, P<0.05) and impaired endothelium-dependent vascular relaxation.

Structured PICO

Does increased vascular superoxide production modulate blood pressure and vascular function in low-renin hypertension induced by DOCA-salt in rats?

P
Population
Rats treated with DOCA and saline drinking water for 3 weeks to induce low-renin hypertension.
I
Intervention
Heparin-binding superoxide dismutase (1200 U/d IV for 3 days) or Losartan (25 mg/kg/d PO for 7 days)
C
Comparator
Control rats
O
Outcome
Systolic blood pressure, aortic superoxide production, and endothelium-dependent vascular relaxation (to acetylcholine and A23187)surrogate

Increased vascular superoxide production impairs endothelium-dependent vascular relaxation but does not modulate blood pressure in low-renin hypertension.

Main Result

Absolute Event Rate: 3972% vs 852%

p-value: p=<0.05

Abstract

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 x kg(-1) x 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.

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Cite This Study

Somers et al. (2000) studied Low-renin hypertension. DOCA and saline drinking water vs. Controls was evaluated on Aortic superoxide production (p=<0.05). DOCA-salt induced low-renin hypertension in rats significantly increased aortic superoxide production (3972 vs 852, P<0.05) and impaired endothelium-dependent vascular relaxation.

synapsesocial.com/papers/6a20d8678446b104fdecb49chttps://doi.org/10.1161/01.cir.101.14.1722
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