Vascular superoxide production and vasomotor function in hypertension induced by deoxycorticosterone acetate-salt

Background-Angiotensin II-induced hypertension is associated with increased vascular superoxide production, which contributes to hypertension caused b y the octapeptide. In cell culture, stretch increases endothelial and vascu lar 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 producti on remain unclear, Furthermore, the role of ROS in vascular function and hy pertension in low-renin hypertension is undefined. Methods and Results-Rats were treated with DOCA and saline drinking water f or 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 in creased compared with controls. Relaxations of vascular segments to acetylc holine (ACh, 100+/-2% versus 75+/-2%, P<0.05) and the calcium ionophore A23 187 (92+/-2% versus 72+/-3%, P<0.05) were also impaired in DOCA-salt, Hepar in binding superoxide dismutase (1200 U/d IV for 3 days) had no effect on b lood pressure but significantly improved relaxations to ACh and A23187. Los artan (25 mg . kg(-1) . d(-1) PO) for 7 days did not correct the hypertensi on 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 prod uction occurs not only in angiotensin II-induced hypertension but also in h ypertension known to be associated with low-renin states. Increased superox ide production alters large-vessel endothelium-dependent vascular relaxatio n but does not modulate blood pressure in low-renin hypertension.