Low-dose angiotensin II increases free isoprostane levels in plasma

Chronic intravenous infusion of subpressor doses of angiotensin II causes b lood pressure to increase progressively over the course of several days. Th e mechanisms underlying this response, however, are poorly understood, Beca use high-dose angiotensin II increases oxidative stress, and some compounds that result from the increased oxidative stress (eg, isoprostanes) produce vasoconstriction and antinatriuresis, we tested the hypothesis that a subp ressor dose of angiotensin II also increases oxidative stress, as measured by 8-epi-prostaglandin F-2 alpha (isoprostanes), which may contribute to th e slow presser response to angiotensin II. To test this hypothesis, we infu sed angiotensin II (10 ng/kg per minute for 28 days via an osmotic pump) in to 6 conscious normotensive female pigs (30 to 35 kg). We recorded mean art erial pressure continuously with a telemetry system and measured plasma iso prostanes before starting the angiotensin II infusion (baseline) and again after 28 days with an enzyme immunoassay. Angiotensin II infusion significa ntly increased mean arterial pressure from 121+/-4 to 153+/-7 mm Hg (P<0.05 ) without altering total plasma isoprostane levels (180.0+/-24.3 versus 147 .0+/-29.2 pg/mL; P=NS). However, the plasma concentrations of free isoprost anes increased significantly, from 38.3+/-5.8 to 54.7+/-10.4 pg/mL (P<0.05) . These results suggest that subpressor doses of angiotensin II increase ox idative stress, as implied by the increased concentration of free isoprosta nes, which accompany the elevation in mean arterial pressure elevation. Thu s, isoprostane-induced vasoconstriction and antinatriuresis may contribute to the hypertension induced by the slow presser responses of angiotensin II .