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.