Low-dose angiotensin II increases free isoprostane levels in plasma.
Chronic intravenous infusion of subpressor doses of angiotensin II causes blood pressure to increase progressively over the course of several days. The mechanisms underlying this response, however, are poorly understood. Because 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 subpressor dose of angiotensin II also increases oxidative stress, as measured by 8-epi-prostaglandin F(2alpha) (isoprostanes), which may contribute to the slow pressor response to angiotensin II. To test this hypothesis, we infused angiotensin II (10 ng/kg per minute for 28 days via an osmotic pump) into 6 conscious normotensive female pigs (30 to 35 kg). We recorded mean arterial pressure continuously with a telemetry system and measured plasma isoprostanes before starting the angiotensin II infusion (baseline) and again after 28 days with an enzyme immunoassay. Angiotensin II infusion significantly 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 isoprostanes 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 oxidative stress, as implied by the increased concentration of free isoprostanes, which accompany the elevation in mean arterial pressure elevation. Thus, isoprostane-induced vasoconstriction and antinatriuresis may contribute to the hypertension induced by the slow pressor responses of angiotensin II.
Haas
J A
JA
Department of Physiology and Biophysics, Mayo School of Medicine and Mayo Clinic, Rochester, MN 55905, USA.
Krier
J D
JD
Bolterman
R J
RJ
Juncos
L A
LA
Romero
J C
JC
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D015237:Dinoprost / Q000031:analogs & derivatives* / Q000097:blood; D028441:F2-Isoprostanes; D005260:Female; D018384:Oxidative Stress; D013552:Swine; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D028441:F2-Isoprostanes; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; C075750:8-epi-prostaglandin F2alpha; D015237:Dinoprost