Exercise training enhances vasodilation responses to vascular endothelial growth factor in porcine coronary arterioles exposed to chronic coronary occlusion.
BACKGROUND
Chronic coronary occlusion (CCO) impairs endothelial function of distal collateral-dependent microvasculature; however, long-term exercise training (EX) seems to improve endothelial dysfunction. We hypothesized that EX enhances vasodilation responses to vascular endothelial growth factor (VEGF165), mediated via nitric oxide (NO), in arterioles exposed to CCO.


RESULTS
The proximal left circumflex coronary artery (LCx) of female Yucatan miniswine was surgically instrumented with an ameroid occluder to induce CCO; 8 weeks after surgery, animals were randomized into 14-week sedentary (SED) or EX (treadmill; 5 d/wk) protocols. Coronary arterioles ( approximately 100 microm in diameter) were isolated from collateral-dependent (LCx) and nonoccluded (left anterior descending; LAD) perfused myocardium of SED and EX animals. Vasodilation was assessed by videomicroscopy and MacLab data acquisition. Responses to VEGF165 were unaffected by EX in nonoccluded LAD arterioles; in contrast, EX markedly enhanced VEGF165-induced vasodilation of collateral-dependent LCx arterioles (P<0.05; EX versus SED). Furthermore, VEGF165-induced vasodilation of EX LCx arterioles exceeded that of EX or SED LAD arterioles (P<0.05). Enhanced vasodilation of EX LCx arterioles was abolished by inhibition of NO synthase and tyrosine kinase activity. Combined inhibition of NO synthase and cyclooxygenase decreased VEGF165-induced vasodilation of all vessels.


CONCLUSIONS
EX enhances VEGF165-induced vasodilation in arterioles distal to CCO; EX effects seem to be mediated through increases in NO.
Fogarty
Jennifer A
JA
Cardiovascular Research Institute and Department of Medical Physiology, Texas A&M University System Health Science Center, College Station, Tex 77843-1114, USA.
Muller-Delp
Judy M
JM
Delp
Michael D
MD
Mattox
Mildred L
ML
Laughlin
M Harold
MH
Parker
Janet L
JL
D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000503:physiopathology; D002908:Chronic Disease; D003097:Collateral Circulation; D003327:Coronary Disease / Q000503:physiopathology*; D003331:Coronary Vessels / Q000187:drug effects / Q000503:physiopathology*; D046508:Culture Techniques; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000503:physiopathology; D009569:Nitric Oxide / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010805:Physical Conditioning, Animal; D011453:Prostaglandins / Q000502:physiology; D011505:Protein-Tyrosine Kinases / Q000502:physiology; D013552:Swine; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*; D019323:omega-N-Methylarginine / Q000494:pharmacology
D004791:Enzyme Inhibitors; D011453:Prostaglandins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D014665:Vasodilator Agents; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D011505:Protein-Tyrosine Kinases