William M. Chilian

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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)
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)
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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)
Peroxynitrite (ONOO(-)) is a contractile agonist of rat middle cerebral arteries. To determine the mechanism responsible for this component of ONOO(-) bioactivity, the present study examined the effect of ONOO(-) on ionic current and channel activity in rat cerebral arteries. Whole cell recordings of voltage-clamped cells were made under conditions designed(More)
e99 V ascular dysfunction is causally contributing to many diseases , including but not limited to cardiovascular disease, which is still the leading cause of death in the Western world. The endothelium that lines the inner wall of the blood vessels plays a critical role in the pathobiology of these illnesses. Particularly after ischemia or injury, the(More)
Tumor vessels are characterized by abnormal morphology and hyperpermeability that together cause inefficient delivery of chemotherapeutic agents. Although vascular endothelial growth factor has been established as a critical regulator of tumor angiogenesis, the role of mechanical signaling in the regulation of tumor vasculature or tumor endothelial cell(More)
Vascular dysfunction is a hallmark of many diseases, including coronary heart disease, stroke, and diabetes. The underlying mechanisms of these disorders are intimately associated with an increase in oxidative stress and excess generation of reactive oxygen species. Here, we report that the anionic free radical, superoxide (O2*- ), directly affects the(More)
The regulation of the coronary circulation is a complex paradigm in which many inputs that influence vasomotor tone have to be integrated to provide the coronary vasomotor adjustments to cardiac metabolism and to perfusion pressure. We hypothesized that the integration of many disparate signals that influence membrane potential of smooth muscle cells,(More)