Journal
VASCULAR PHARMACOLOGY
Volume 46, Issue 4, Pages 253-259Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.vph.2006.10.009
Keywords
nitric oxide (NO); prostacyclin (PGI(2)); endothelial factors; vascular endothelial growth factor (VEGF); acetylcholine; radial artey; internal mammary
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Objectives: Due to the potential therapeutic value of vascular endothelial growth factor (VEGF) in coronary artry disease, the effect and mechanism of VEGF in human arteries used as coronary bypass grafts become important but not fully understood. VGEF-mediated endothelial regulation in vasorelaxation was studied in internal mammary artery (IMA) and radial artery (RA), compared with that of the classical agent-acetylcholine (ACh). The role of nitric acid (NO), prostacyclin (PGI(2)), and endothelium-derived hyperpolarizing factor (EDHF) was investigated. Methods: VEGF- and ACh-induced responses were measured in RA and IMA with or without endothelium and in the absence or presence of inhibitors of nitric oxide synthase or prostacyclin. In addition, the VEGF-induced PGI(2) was measured by enzyme immunoassay. Results: VEGF induced similar relaxation in RA (59.2 +/- 9.3%) and IMA (56.1 +/- 6.4%) that was significantly inhibited by N-omega-nitro-L-arginine (L-NNA) plus oxyhemoglobin (HbO) (IMA: 24.9 +/- 4.3%, P = 0.03 vs. RA: 25.0 +/- 8.6%, P = 0.01) or by indomethacin (INDO) (IMA: 21.8 +/- 2.5%,P = 0.000 vs. RA: 30.0 +/- 6.6%, P = 0.04) with more inhibition in IMA than RA (P < 0.05). In addition, the VEGF- induced PGI(2) was significantly higher in IMA than RA (11.5 +/- 2.1 vs. 4.9 +/- 1.1 pg/ml/mg, P = 0.002). INDO + L-NNA + HbO reduced the VEGF-induced relaxation to 20.8 +/- 4.6% in RA vs. 4.8 +/- 1.6% in IMA (P = 0.01). In contrast, the maximal relaxation induced by ACh in RA (55.9 +/- 6.0%) and IMA (48.5 +/- 5.3%) was largely inhibited by L-NNA in IMA and RA (14.7 +/- 3.0%, P = 0.000 vs. 15.2 +/- 3.2%, P = 0.004) but little affected by INDO. Conclusions: VEGF induces similar relaxation in IMA and RA with significantly more PGI(2)-mediated relaxation and higher stimulated PGI(2) level in IMA but more EDHF-mediated relaxation in RA. In comparison, ACh-induced relaxation mainly depends on NO. Thus, our study reveals a significant difference in the mechanism of the endothelium-dependent relaxation induced by VEGF and ACh. (c) 2006 Elsevier Inc. All rights reserved.
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