Premium
Impaired endothelial relaxation and enhanced endothelial contraction and microvascular ADMA in angiotensin II infused rats: effects of tempol
Author(s) -
Wang Dan,
Luo Zaiming,
Welch William J,
Aslam Shakil,
Teerlink Tom,
Wilcox Christopher S
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.lb552
Subject(s) - endocrinology , medicine , asymmetric dimethylarginine , endothelial dysfunction , myograph , chemistry , angiotensin ii , contraction (grammar) , nitric oxide , vasodilation , reactive oxygen species , malondialdehyde , endothelium , oxidative stress , blood pressure , arginine , biochemistry , amino acid
Since angiotensin II (Ang II) causes endothelial dysfunction, we investigated if it increased microvascular reactive oxygen species (ROS) or asymmetric dimethylarginine ADMA) and switches endothelial function from vasodilator to vasoconstrictor pathways. Acetylcholine‐induced endothelium dependent responses of mesenteric resistance arterioles (MRAs) were assessed in a myograph and vascular nitric oxide (NO) and ROS by fluorescent probes in groups (n=6) of male rats infused for 14 days with Ang II (200 ng/kg/min) or vehicle alone or with oral tempol (2mmol/L, a radical scavenger). Ang II infusion increased blood pressure and plasma malondialdehyde (0.3±0.1 vs 0.6 ±0.02, p<0.01) and decreased endothelium derived relaxation (18±5 vs 54±6%, p<0.01) and hyperpolarizing (19±3 vs 29±3%, p<0.05) responses and NO activity (0.9±0.1 vs 1.6±0.2%, p<0.01) yet enhanced endothelium dependent contraction response (23±5 vs 5±5%, p<0.05) and ROS (0.82±0.05 vs 0.15±0.03 units; p<0.01). Ang II decreased the expression of dimethylarginine dimethylaminohydrolase‐2 and increased ADMA in MRAs (450±50 vs 260±35 pmol/mg protein, p<0.01) but not in plasma. Tempol prevented all these responses. In conclusion, Ang II infusion redirected endothelial responses from relaxation to contraction with a reduction in vascular NO and an increase in ROS and ADMA. These are dependent on ROS and could contribute to hypertension.