Specific alterations of endothelial signal transduction pathways of porcine epicardial coronary arteries in left ventricular hypertrophy.
Coronary endothelial dysfunction in left ventricular hypertrophy (LVH) can reduce myocardial perfusion and result in an impaired global LV function. The objective of this study was to characterize the specific alterations of endothelial signal transduction of coronary arteries in a swine LVH model. Aortic banding was performed 3 cm above the coronary ostia. Vascular reactivity studies were performed to assess the nitric oxide (NO) and the EDHF-mediated relaxations. There was a significant increase in LV/body weight ratio associated with an increased in LV diastolic and end-diastolic pressure and decrease in dP/dT (P < 0.05), with no significant difference in coronary pressures 60 days after pressure-overload LVH. There was a significant decrease in endothelium-dependent relaxations to serotonin (5-HT) and to bradykinin (BK) (P < 0.05 for both) from LVH animals. There was no significant decrease of relaxations in the presence of BK and Nomega-l-arginine (EDHF pathway). Plasma NO(x) levels decreased significantly from 1.8% +/- 0.2% to 1.2% +/- 0.1% (P < 0.05 versus control). Chronic pressure-overload LVH is associated with an endothelial dysfunction involving both Gi and Gq protein-mediated relaxations in coronary arteries as well as the EDHF pathway.
Malo
Olivier
O
Research Center, Department of Pharmacology, Montreal Heart Institute, 5000 Belanger Street East, Montreal, Quebec H1T 1C8, Canada.
Carrier
Michel
M
Shi
Yan Fen
YF
Tardif
Jean-Claude
JC
Tanguay
Jean-Francois
JF
Perrault
Louis P
LP
D000818:Animals; D001685:Biological Factors / Q000502:physiology*; D001794:Blood Pressure; D003331:Coronary Vessels / Q000187:drug effects; D005260:Female; D017379:Hypertrophy, Left Ventricular / Q000000981:diagnostic imaging / Q000503:physiopathology*; D008297:Male; D008955:Models, Cardiovascular; D009569:Nitric Oxide / Q000096:biosynthesis / Q000494:pharmacology / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013552:Swine; D014463:Ultrasonography
D001685:Biological Factors; C067410:endothelium-dependent hyperpolarization factor; D009569:Nitric Oxide