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To determine the distribution of resistance in the coronary vasculature, measurements of microvascular pressure and diameter were obtained with vasomotor tone intact and during coronary dilation produced by papaverine. We studied anesthetized, open-chest cats and used jet ventilation synchronized to the cardiac cycle to eliminate respiratory-induced cardiac(More)
Assessment of coronary blood flow and the vasodilator reserve capacity of individual coronary arteries in the catheterization laboratory has been hampered by methodologic limitations. We have developed and validated a small Doppler catheter that can subselectively measure phasic coronary blood flow velocity (CBFV). In seven anesthetized calves, CBFV was(More)
Hydrogen peroxide (H(2)O(2)) is a proposed endothelium-derived hyperpolarizing factor and metabolic vasodilator of the coronary circulation, but its mechanisms of action on vascular smooth muscle remain unclear. Voltage-dependent K(+) (K(V)) channels sensitive to 4-aminopyridine (4-AP) contain redox-sensitive thiol groups and may mediate coronary(More)
BACKGROUND We hypothesized that the inflammatory cytokine tumor necrosis factor-alpha (TNF) produces endothelial dysfunction in type 2 diabetes. METHODS AND RESULTS In m Lepr(db) control mice, sodium nitroprusside and acetylcholine induced dose-dependent vasodilation, and dilation to acetylcholine was blocked by the NO synthase inhibitor(More)
This study assessed the redistribution of coronary microvascular resistance during vasodilation produced by dipyridamole. Measurements of microvascular diameter and pressure in the beating left ventricle of anesthetized cats were accomplished by means of a computer-controlled system that enabled measurements in the beating heart. Resistances of coronary(More)
Flow-mediated dilation has been documented in large conduit coronary arteries but not in coronary arterioles. The goal of this study was to determine whether this response occurs in coronary arterioles and whether it competes with myogenic constriction. Subepicardial arterioles (40-80 microns) were isolated and cannulated with two glass micropipettes(More)
OBJECTIVE We tested the hypothesis that hydrogen peroxide (H2O2), the dismutated product of superoxide (O2*-), couples myocardial oxygen consumption to coronary blood flow. Accordingly, we measured O2*- and H2O2 production by isolated cardiac myocytes, determined the role of mitochondrial electron transport in the production of these species, and determined(More)
There is a need to develop new and more consistent animal models of cardioprotection. Traditionally, outbred dogs, rabbits, and rats have been studied. We determined resistance to ischemia in isolated hearts from inbred strains of rats. Hearts from inbred rats: SS/Mcw (Dahl S, Dahl salt-sensitive), DA/Hsd (Dark Agouti), LEW/Hsd (Lewis), and BN/SsN/Mcw(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)
BACKGROUND A deficit in the endothelial production of nitric oxide (NO) is associated with the sequelae of reperfusion injury. Because endothelial NO synthesis depends on the cofactor tetra-hydrobiopterin (BH4), we hypothesized that depletion of this cofactor underlies the reduction of endothelium-dependent dilation in reperfusion injury. METHODS AND(More)