Role of RAS inhibition in the regulation of Cu/Zn-SOD in the cardiac and peripheral arterial beds in humans.
Inhibition of the renin-angiotensin system (RAS) improves hemodynamics and may ameliorate oxidative stress in heart failure (HF). Through activation of nicotinamide adenine dinucleotide phosphate oxidase, angiotensin II induces superoxide, which is primarily cleared by cytosolic copper-zinc superoxide dismutase (Cu/Zn-SOD). We examined the interdependency of hemodynamics and levels of Cu/Zn-SOD and oxidized low-density lipoprotein (oxLDL) in HF patients, using a randomized, double-blinded, crossover design to compare (i) the outcomes of single-agent therapy with either benazepril or valsartan alone vs. the combination thereof and (ii) the outcome of single-agent treatment with benazepril vs. single-agent treatment with valsartan. After each treatment, arterial (ART) and coronary sinus (CS) blood samples were collected. Cu/Zn-SOD and oxLDL levels were higher in CS samples than in ART samples. Furthermore, patients under combined treatment exhibited the highest CS levels of Cu/Zn-SOD, whereas there was no significant difference between the groups on either benazepril or valsartan alone. This finding suggests an augmentation of the cardiac antioxidative potential under more complete RAS inhibition. Cu/Zn-SOD and oxLDL levels correlated with measures of afterload rather than preload, which in turn suggests a beneficial effect of afterload reduction on oxidative stress in HF.
Kuster
G M
GM
Department of Biomedicine, University Hospital Basel, Basel, Switzerland. gkuster@uhbs.ch
Nietlispach
F
F
Kiowski
W
W
Schindler
R
R
Bernheim
A
A
Schuetz
P
P
Mueller
B
B
Morgenthaler
N G
NG
Rüter
F
F
Riesen
W
W
Rickli
H
H
Brunner-La Rocca
H P
HP
D000328:Adult; D000368:Aged; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D001552:Benzazepines / Q000008:administration & dosage / Q000494:pharmacology*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D008077:Lipoproteins, LDL / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects; D012084:Renin-Angiotensin System / Q000187:drug effects*; D013482:Superoxide Dismutase / Q000187:drug effects* / Q000378:metabolism; D013777:Tetrazoles / Q000008:administration & dosage / Q000494:pharmacology*; D014633:Valine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D000068756:Valsartan
D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D001552:Benzazepines; D008077:Lipoproteins, LDL; D013777:Tetrazoles; C099252:oxidized low density lipoprotein; D000068756:Valsartan; D013482:Superoxide Dismutase; D014633:Valine; C044946:benazepril