Increased inactivation of nitric oxide is involved in coronary endothelial dysfunction in heart failure.
Recent evidence suggests the possibility that enhanced inactivation of endothelium-derived nitric oxide (NO) by oxygen free radical (OFR) may cause endothelial dysfunction in heart failure (HF). To test this hypothesis, we examined the effect of antioxidant therapy on endothelium-dependent vasodilation of the coronary circulation in a canine model of tachycardia-induced HF. Endothelium-dependent vasodilation was less than that in controls, and OFR formation in coronary arterial and myocardial tissues was greater in HF dogs than those in controls. The immunohistochemical staining of 4-hydroxy-2-nonenal, OFR-induced lipid peroxides was detected in coronary microvessels of HF dogs. Intracoronary infusion of the cell-permeable OFR scavenger Tiron inhibited OFR formation and improved endothelium-dependent vasodilation in HF dogs but not in controls. The NO synthesis inhibitor N(G)-monomethyl-L-arginine (L-NMMA) diminished the beneficial effect of Tiron in HF dogs. Endothelium-independent vasodilation was similar between control and HF dogs, and no change in its response was noted by Tiron or Tiron plus L-NMMA in either group. In summary, antioxidant treatment with Tiron improved coronary vascular endothelium-dependent vasodilation by increasing NO activity in tachycardia-induced HF. Thus coronary endothelial dysfunction in HF may be, at least in part, due to increased inactivation of NO by OFR.
Arimura
K
K
Department of Cardiovascular Medicine, Kyushu University Graduate School of Medicine, Fukuoka, 812-8582 Japan.
Egashira
K
K
Nakamura
R
R
Ide
T
T
Tsutsui
H
H
Shimokawa
H
H
Takeshita
A
A
D014013:1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt / Q000494:pharmacology; D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D003331:Coronary Vessels / Q000503:physiopathology*; D004285:Dogs; D004452:Echocardiography; D004558:Electric Stimulation; D004730:Endothelium, Vascular / Q000503:physiopathology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005609:Free Radicals / Q000378:metabolism; D006333:Heart Failure / Q000503:physiopathology*; D006439:Hemodynamics / Q000187:drug effects; D007150:Immunohistochemistry; D007202:Indicators and Reagents; D015227:Lipid Peroxidation; D009569:Nitric Oxide / Q000378:metabolism / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D052250:Nitric Oxide Synthase Type III; D019323:omega-N-Methylarginine / Q000494:pharmacology
D004791:Enzyme Inhibitors; D005609:Free Radicals; D007202:Indicators and Reagents; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D014013:1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; D000109:Acetylcholine