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Effects of nitric oxide and superoxide on relaxation in human artery and vein
C A Hamilton1, G Berg, M Mcintyre
1Department of Medicine and Therapeutics, University of Glasgow, UK.
Insights
Internal thoracic artery (ITA) and saphenous vein (SV) function differently in coronary artery bypass graft surgery (CABG). Reduced nitric oxide release in SV may explain lower graft patency rates compared to ITA.
Area of Science:
- Vascular Biology
- Cardiovascular Surgery
- Biochemistry
Background:
- Endothelium-derived factors are crucial for graft patency in coronary artery bypass graft surgery (CABG).
- Internal thoracic artery (ITA) exhibits superior long-term patency compared to saphenous vein (SV) conduits.
- Understanding the roles of nitric oxide and superoxide in ITA and SV function is vital for improving CABG outcomes.
Purpose of the Study:
- To investigate the effects of nitric oxide and superoxide on vascular relaxation in isolated ITA and SV rings.
- To compare nitric oxide synthesis and release between ITA and SV in patients undergoing CABG.
- To elucidate the mechanisms underlying the differential patency rates of ITA and SV grafts.
Main Methods:
- Isolated ITA and SV rings were used to assess vascular relaxation responses.
- Nitric oxide synthesis was inhibited using NG-nitro-L-Argenine methylester (L-NAME).
- Superoxide levels were modulated using superoxide dismutase (SOD) and tiron; endothelial nitric oxide synthase (eNOS) expression was evaluated via immunocytochemistry.
Main Results:
- Both ITA and SV demonstrated stimulated nitric oxide release, but basal release was diminished in SV.
- Superoxide scavenging with SOD and tiron enhanced carbachol-stimulated relaxation in both vessels.
- Tiron treatment significantly increased basal nitric oxide in SV, and eNOS immunoreactivity was higher in ITA than SV.
Conclusions:
- Reduced basal nitric oxide production and potentially lower eNOS expression in SV may contribute to its inferior graft patency compared to ITA.
- Modulating nitric oxide and superoxide levels can impact vascular relaxation in both conduit types.
- These findings offer insights into optimizing graft selection and function in CABG procedures.
Abstract:
Endothelium-derived relaxing and contracting factors play an important role in atherosclerosis, re-stenosis and graft survival. Internal thoracic artery (ITA) and saphenous vein (SV) are used as conduit vessels in coronary artery bypass graft surgery (CABG). The long-term graft patency rate is higher with ITA than SV. Effects of nitric oxide and superoxide on vascular relaxation in isolated rings of ITA and SV from patients undergoing CABG were investigated. NG-nitro-L-Argenine methylester (L-NAME) was used to block nitric oxide synthesis and superoxide dismutase (SOD) and tiron to scavenge superoxide. Responses to carbachol were taken as a measure of stimulated nitric oxide release and increased responses to phenylephrine after addition of L-NAME as a measure of basal nitric oxide release. Immunocytochemical demonstration of endothelial nitric oxide synthase was performed using anti-endothelial nitric oxide synthetase (anti-eNOS) NOS antibody. Stimulated nitric oxide release was observed in ITA and SV but basal release was reduced or absent in SV. Treatment with SOD and tiron potentiated carbachol stimulated relaxation in ITA and SV. Tiron treatment resulted in a significant increase in basal nitric oxide in veins. eNOS immunoreactivity was more intense in ITA than SV, compatible with reduced nitric oxide production in veins. This may contribute to the reduced patency of venous grafts.