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Background: The relationship between coronary remodeling, shear stress and endothelial function remains unclear., Objective: The present study investigated the effects of mechanical factors on structure and function of epicardial coronary arteries., Methods: Patients (group 1: %area stenosis<40%, n=55; or group 2: %area stenosis>or=40%, n=17) with a discrete mildly stenotic lesion (%diameter stenosis<30%) underwent intravascular ultrasound examination of the left anterior descending coronary artery for determination of vessel area, lumen area, plaque area, cross-sectional areas at reference segments, and remodeling index (the ratio of vessel area at the culprit lesion to vessel area at the proximal reference site). Further, vascular reactivity was examined using intracoronary administration of acetylcholine, papaverine, and nitroglycerin., Results: Vessel area significantly correlated with plaque area in both groups (r=0.65, P<0.0001 and r=0.85, P<0.0001). Group 1 showed significantly greater acetylcholine-induced percentage changes in coronary blood flow (67+/-70 vs. 16+/-75%, P<0.05) and coronary artery diameter (-7+/-18 vs.-32+/-31%, P<0.01) and also significantly smaller coronary wall shear stress (65+/-27 vs. 81+/-32 dynes/cm, P<0.05) than group 2. The percentage increase in coronary blood flow induced by acetylcholine was significantly and positively correlated with remodeling index in group 1 (r=0.64, P<0.0001) but not in group 2 (r=-0.03, P=0.90) and was also significantly and positively correlated with coronary wall shear stress in group 1 (r=0.46, P<0.001) but not in group 2 (r=-0.33, P=0.19)., Conclusions: Endothelium-dependent vasodilation in the resistance coronary artery correlates with remodeling via increased wall shear stress when target lesions %area stenosis is <40%.

In cultured endothelial cells, estrogen increases expression and activity of endothelial nitric oxide synthase (eNOS). This study was designed to determine whether estrogenic treatments increase eNOS similarly in vivo. Aortic endothelial cells were collected from adult ovariectomized pigs which were untreated (8wk-OVX) or treated with oral 17beta-estradiol (E2, 2 mg/day), conjugated equine estrogen (CEE, 0.625 mg/day), or raloxifene (60 mg/day) for 4 weeks. Plasma NOx, estrogen receptors (ERalpha and ERbeta), eNOS, eNOS regulatory proteins, and eNOS mRNA in endothelial cells were determined by Griess reaction, Western blot, and real-time polymerase chain reaction, respectively. Ovariectomy decreased, whereas all treatments restored plasma NO(x) to pre-OVX levels. On the contrary, eNOS protein and mRNA increased with ovariectomy; E2 and CEE but not raloxifene reduced mRNA; eNOS protein was reduced by CEE and raloxifene treatments. Tyrosine phosphorylation of eNOS and expression of calmodulin increased, but Hsp90 decreased with all treatments and only raloxifene treatment increased caveolin-1 compared with OVX. Expression of ERalpha/ERbeta increased with ovariectomy and was reversed by treatments such that raloxifene>CEE>E2. Three clinically relevant estrogen treatments restore plasma NO after ovariectomy, but do not affect eNOS mRNA, posttranslational regulation of eNOS or expression of estrogen receptors in the same way.

Objectives: To characterize delayed restoration of coronary blood flow following successful percutaneous transluminal coronary angioplasty (PTCA)., Background: Delayed restoration of coronary blood flow following successful PTCA is common and likely the result of multiple factors. Temporary myocardial ischemia and dipyridamole administration both result in increased coronary blood flow, but by different mechanisms. The relationship between these phenomena and exercise-induced ST-segment depression after PTCA was investigated to determine if any correlation existed., Methods: Forty consecutive patients with single-vessel coronary artery disease underwent treadmill exercise testing before and after PTCA. The percentage change in coronary blood flow before and after 90 s balloon inflation was assessed. After a new steady state had been reached, dipyridamole was infused and changes in coronary blood flow were again determined. The relationship between changes in coronary blood flow and the presence of ST-segment depression during exercise testing after PTCA was determined., Results: Peak coronary blood flow induced by reactive hyperemia was significantly greater than that in the steady state after balloon inflation (48.5+/-38.8 compared with 15.1+/-13.2 ml/min, P<0.0001). Dipyridamole administration also resulted in significant increases in coronary blood flow (15.1+/-13.2 ml/min compared with 31.0+/-24.9 ml/min, P<0.0001). ST-segment depression after PTCA was significantly less than before (0.10+/-0.07 mV compared with 0.19+/-0.08 mV, P<0.001). Further, reactive hyperemia, but not dipyridamole-induced hyperemia, correlated with attenuation of exercise-induced ST-segment depression after PTCA (r=0.62, P<0.0001)., Conclusions: Reactive hyperemia following temporary coronary occlusion recreates local conditions associated with delayed resolution of myocardial ischemia following successful PTCA. Further, this phenomenon appears to be distinct from changes in coronary blood flow induced by dipyridamole.