Increased inactivation of nitric oxide is involved in coronary endothelial dysfunction in heart failure.

Abstract

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.

• Authors: K Arimura, K Egashira, R Nakamura, T Ide, H Tsutsui, H Shimokawa, A Takeshita
• Journal: American journal of physiology. Heart and circulatory physiology (Am J Physiol Heart Circ Physiol) Vol. 280 Issue 1 Pg. H68-75 (Jan 2001) ISSN: 0363-6135 [Print] United States
• PMID: 11123219 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Enzyme Inhibitors
• Free Radicals
• Indicators and Reagents
• omega-N-Methylarginine
• Nitric Oxide
• 1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt
• Nitric Oxide Synthase
• Nitric Oxide Synthase Type III
• Acetylcholine

Topics

• 1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt (pharmacology)
• Acetylcholine (pharmacology)
• Animals
• Coronary Vessels (physiopathology)
• Dogs
• Echocardiography
• Electric Stimulation
• Endothelium, Vascular (physiopathology)
• Enzyme Inhibitors (pharmacology)
• Free Radicals (metabolism)
• Heart Failure (physiopathology)
• Hemodynamics (drug effects)
• Immunohistochemistry
• Indicators and Reagents
• Lipid Peroxidation
• Nitric Oxide (metabolism, physiology)
• Nitric Oxide Synthase (antagonists & inhibitors)
• Nitric Oxide Synthase Type III
• omega-N-Methylarginine (pharmacology)