Acute angiotensin II increases plasma F2-isoprostanes in salt-replete human hypertensives.
Angiotensin (Ang) II induces oxidative stress in vitro and in animal models of hypertension. We tested the hypothesis that Ang II increases oxidative stress in human hypertension, as assessed by plasma F2-isoprostane concentrations. Plasma F2-isoprostanes, hemodynamic and endocrine parameters were measured at baseline and following a 55 min infusion of 3 ng/kg/min Ang II in 13 normotensive and 13 hypertensive volunteers ingesting a high- (200 mmol/d) or low- (10 mmol/d) sodium diet. Mean arterial pressure (MAP) and body mass index were higher in hypertensive subjects. Ang II infusion increased MAP (p<.001) and plasma aldosterone concentrations (p<.001) and decreased plasma renin activity (p<.001) and renal plasma flow (p<.001) to a similar extent in both groups. Plasma F2-isoprostane concentrations were similar at baseline. There was no effect of Ang II on F2-isoprostane concentrations during low-salt intake in either group (normotensive 51.7 +/- 7.1 to 53.7 +/- 6.5 pg/ml and hypertensive 52.2 +/- 8.2 to 56.2 +/- 10.0 pg/ml; mean +/- SE). During high-salt intake, Ang II increased F2-isoprostane concentrations in the hypertensive group (52.3 +/- 7.2 to 63.2 +/- 10.4 pg/ml, p=0.010) but not in the normotensive group (54.2 +/- 4.4 to 58.9 +/- 6.6 pg/ml, p=0.83). Acute Ang II infusion increases oxidative stress in vivo in hypertensive humans. The renin-angiotensin system may contribute to oxidative stress in human cardiovascular disease.
Division of Clinical Pharmacology, Departments of Medicine and Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, USA. laine.murphey@vanderbilt.edu
Laine J
LJ
Murphey
Jason D
JD
Morrow
Pairunyar
P
Sawathiparnich
Gordon H
GH
Williams
Douglas E
DE
Vaughan
Nancy J
NJ
Brown
D000328:Adult; D000450:Aldosterone / Q000097:blood; D000804:Angiotensin II / Q000494:pharmacology*; D015415:Biomarkers / Q000097:blood / Q000652:urine; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D004347:Drug Interactions; D028441:F2-Isoprostanes / Q000097:blood* / Q000652:urine; D005260:Female; D006801:Humans; D006973:Hypertension / Q000097:blood*; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D012965:Sodium Chloride / Q000008:administration & dosage / Q000494:pharmacology*
D015415:Biomarkers; D028441:F2-Isoprostanes; D000804:Angiotensin II; D012965:Sodium Chloride; D000450:Aldosterone