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Background—Despite the importance of endothelial function for coronary regulation, there is little information and virtually no consensus about the causal mechanisms of endothelial dysfunction in myocardial ischemia/reperfusion (I/R) injury. Because tumor necrosis factor-␣ (TNF-␣) is reportedly expressed during ischemia and can induce vascular inflammation(More)
Conventionally, ischemic heart disease (IHD) is equated with large vessel coronary disease. However, recent evidence has suggested a role of compromised microvascular regulation in the etiology of IHD. Because regulation of coronary blood flow likely involves activity of specific ion channels, and key factors involved in endothelium-dependent dilation, we(More)
RATIONALE In the working heart, coronary blood flow is linked to the production of metabolites, which modulate tone of smooth muscle in a redox-dependent manner. Voltage-gated potassium channels (Kv), which play a role in controlling membrane potential in vascular smooth muscle, have certain members that are redox-sensitive. OBJECTIVE To determine the(More)
Ischemic injury to the kidney results in blood vessel loss and predisposition to chronic renal disease. Angiostatin is a proteolytic cleavage product of plasminogen that inhibits angiogenesis, promotes apoptosis of endothelial cells, and disrupts capillary integrity. A combination of lysine-Sepharose enrichment followed by Western blotting was used to study(More)
The goals of this study were 1) to quantitate the effects of atherosclerosis on physiological and pharmacological endothelium-dependent vasoactive responses in coronary arterioles downstream from arterial lesions and 2) to determine if administration of L-arginine, the precursor for endothelium-derived was induced in pigs, and vasomotor responses of(More)
Background. The purpose of this study was to determine whether endothelium-dependent relaxation competes with avl-and a*-adrenergic coronary microvascular constriction in the beating heart in vivo. Methods and Results. Coronary microvascular diameters were measured using stroboscopic epi-illumination and intravital microscopy during fluorescein(More)
BACKGROUND We hypothesized that ischemia-induced expression of vascular endothelial growth factor (VEGF) and the production of NO stimulate coronary collateral growth. METHODS AND RESULTS To test this hypothesis, we measured coronary collateral blood flow and VEGF expression in myocardial interstitial fluid in a canine model of repetitive myocardial(More)
BACKGROUND The in vivo mechanism by which inhibition of NO synthase impairs ischemia-induced coronary vascular growth is unknown. We hypothesized that production of the growth inhibitor angiostatin increases during decreased NO production, blunting angiogenesis and collateral growth. METHODS AND RESULTS Measurements were made in myocardial tissue or(More)
BACKGROUND The goal of this study was to determine whether the expression of vascular endothelial growth factor (VEGF) is critical for coronary collateral growth. Previous studies have provided an association between coronary collateral growth and VEGF, but none have allowed determination of a causal role. METHODS AND RESULTS We measured coronary(More)
Studies of the coronary circulation have divided vascular resistances into three large components: large vessels, small resistance vessels, and veins. Studies of the epicardial microcirculation in the beating heart using stroboscopic illumination have suggested that resistance is more precisely controlled in different segments of the circulation.(More)