Nitric oxide produced by endothelial cells increases production of eicosanoids through activation of prostaglandin H synthase.

The endothelium serves many functional roles, including the modulation of vascular smooth muscle tone through the release of vasoactive agents such as nitric oxide (NO) and the eicosanoids. We proposed that NO produced by endothelial cells would increase the production of eicosanoids through enhanced expression and/or activation of prostaglandin H synthase. NO and eicosanoid synthesis were stimulated in a bovine coronary microvessel endothelial cell line with the calcium ionophore A23187 (1 mumol/L).

Sodium butyrate stimulation of HIV-1 gene expression: a novel mechanism of induction independent of NF-kappa B.

Nuclear factor-kappa B (NF-kappa B) has been shown to play a central role in stimulating human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR)-directed viral gene expression. We have previously described a cell line (TE671/RD) that fails to respond to phorbol myristate acetate (PMA) or tumor necrosis factor-alpha (TNF-alpha) in terms of amplifying HIV-1 LTR-driven gene expression unless it is concurrently treated with sodium butyrate. It was not determined whether this lack of response stemmed from an inability of these cells to produce free NF-kappa B or from ineffectual interaction of this sequence-specific transcriptional factor with its target.

Endothelium-mediated control of coronary vascular tone after chronic exercise training.

The purpose of this paper is to examine the role of endothelium-derived relaxing factors in the control of coronary vascular resistance in conditioned subjects (i.e., after exercise training for a period of time sufficient to complete adaptation processes).

Endothelium-dependent vasodilation of proximal coronary arteries from exercise-trained pigs.

We recently reported that alpha-adrenergic vasoconstriction is blunted and adenosine-induced vasodilation is enhanced in proximal coronary arteries of exercise-trained miniature swine [C. L. Oltman, J.

Restenosis following placement of an intracoronary heparin treated tantulum stent in the hyperlipidemic miniature swine model.

Restenosis persists as an important factor limiting a favorable long term outcome following mechanical revascularization. The objective of the present study was to compare the effects of an intracoronary heparin treated tantalum prototype stent and balloon angioplasty on intimal hyperplasia, luminal diameter, and thrombosis in a porcine restenosis model. Male miniswine maintained on a high cholesterol diet and 325 mg aspirin per day underwent cardiac catheterization and oversized balloon injury to the right and left circumflex coronary arteries.

Rat aortic vasoreactivity is altered by old age and hindlimb unloading.

Prolonged bed rest in young adults leads to a number of cardiovascular alterations, including orthostatic intolerance and decreased exercise capacity. Similar changes occur with advanced age. These modifications of cardiovascular function have been suggested to be causally related to changes in peripheral vascular reactivity.

Exercise training alters aortic vascular reactivity in hypothyroid rats.

Hypothyroidism induces a number of cardiovascular adaptations in rats, including decreases in blood flow to high-oxidative skeletal muscle and increases in total peripheral resistance. Conversely, exercise training results in elevations in blood flow to high-oxidative skeletal muscle and decreases in vascular resistance. The purpose of this study was to determine whether hypothyroidism induces changes in the vasomotor responses of arterial vessels and whether exercise training modifies these responses.

Exercise training alters the Ca2+ and contractile responses of coronary arteries to endothelin.

We tested the hypothesis that alterations in myoplasmic free Ca2+ (Ca(m)) regulation in coronary smooth muscle after exercise training (Ex) underlie changes in vasomotor function. Yucatan miniature pigs were endurance trained by treadmill running for 16-20 wk. Simultaneous determination of Ca(m) (fura-2 microfluorometry) and contraction during endothelin exposure in coronary arteries were then performed.

Effects of hyperthyroidism on muscle blood flow during exercise in rats.

Hyperthyroidism is associated with exercise intolerance. Previous research, however, has shown that cardiac output is either normal or enhanced during exercise in the hyperthyroid state. We therefore hypothesized that blood flow to working skeletal muscle is augmented in hyperthyroid animals during in vivo submaximal exercise and, consequently, that noncardiovascular factors are responsible for intolerance to exercise.

Effect of substrate on mitochondrial NADH, cytosolic redox state, and phosphorylated compounds in isolated hearts.

The effect of metabolic substrates on the relation among cytosolic redox state (NADHc/NAD+) mitochondrial NADH (NADHm), and [ATP]/([ADP] x [Pi]) was studied in isolated working rabbit hearts. Substrates were varied from 5.6 mM glucose alone to glucose in combination with 10 mM lactate and/or 10 mM pyruvate while afterload and preload were held constant.

The relationship between phosphorylation potential and redox state in the isolated working rabbit heart.

The effects of the cytosolic and mitochondrial redox state on the function and phosphorylation potential of working perfused rabbit hearts were studied. Hearts were perfused with glucose, while lactate, aminooxy-acetate (an inhibitor of the malate-aspartate shuttle), beta-hydroxybutyrate, and pyruvate were sequentially added to the perfusate to manipulate the cytosolic and mitochondrial NAD+/NADH ratio. The phosphorylation potential and product of ADP and P(i) were both found to be proportional to mitochondrial redox state.

Parameter identification in coronary pressure flow models: a graphical approach.

The confident identification of parameters is important in the practical application of physiological models. However, the task of parameter identification is often complicated by interactions among parameters and by the fact that the sensitivity of the model to changes in a given parameter is generally a function of all the other parameters. Here we illustrate a graphical approach to parameter identification that allows the modeler to visualize the behavior of the model, the sensitivity functions, and certain functions characteristic of parameter interdependence.

Regional changes in capillary supply in skeletal muscle of interval-sprint and low-intensity, endurance-trained rats.

Objective: Exercise training produces regional increases in blood flow capacity among muscle fibers that experience increased activity during exercise. We tested the hypothesis that this increase is partially due to capillary angiogenesis among muscle fibers with large increases in activity during exercise training bouts.

Methods: Two training programs were evaluated: a program consisting of 10-12 weeks of exposure to low-intensity (30 m/min, 0 incline, 60 min/day) (LET) exercise bouts, 5 days/week, and a second program consisting of 8-10 weeks of exposure to repetitive bouts (6/day) of sprint (60 m/min, 15% incline) exercise, alternating running (2.

Effects of exercise training on regulation of tone in coronary arteries and arterioles.

A large number of studies now support the concept that exercise training alters functional control of the coronary circulation. Recent work has approached this area using ex vivo coronary arterial preparations (proximal coronary arteries, near-resistance arteries, resistance arterioles) isolated from exercise-trained animals and contracting independently of confounding in vivo influences. The combined results of these studies indicate that training-induced alterations in vascular control mechanisms do not occur uniformly throughout the coronary vascular tree.

Exercise training-induced increase in coronary transport capacity.

The objective of this study was to measure effects of exercise training on coronary flow heterogeneity, microvascular transport, and hemodynamics. Five miniature swine were trained on a treadmill (ET) for 16 wk; five control pigs (C) were confined to cages for the same period. At the end of that period we used the multiple indicator dilution method to measure permeability-surface area product (PS) to EDTA over a range of flow (F) in an anesthetized, open-chest preparation.

Altered control of calcium in coronary smooth muscle cells by exercise training.

The increase in myoplasmic free Ca (Cam) is a primary trigger of contraction in vascular smooth muscle. We review data showing that the sarcoplasmic reticulum (SR) can buffer (attenuate) increases in Cam by: 1) sequestering a fraction of Ca entering the cell via sarcolemmal influx pathways, and 2) slowly releasing Ca from the SR toward the sarcolemma for extrusion from the cell, thereby decreasing subsequent agonist-induced Cam transients and contraction--so called "SR Ca unloading." Endurance exercise trained (EX), not sedentary (SED), Yucatan miniature pigs show SR Ca unloading via a ryanodine-sensitive SR Ca release pathway.

Effects of exercise training on coronary circulation: introduction.

The purpose of this symposium was to evaluate the hypothesis that the beneficial effects of training are the result of training-induced adaptations in the coronary circulation. The approach is to review, summarize, and evaluate data concerning the effects of exercise training on the coronary circulation. Results indicate that aerobic exercise training induces an increase in both blood flow capacity and capillary exchange capacity.

Capillary blood transit time in muscles in relation to body size and aerobic capacity.

The mean minimal transit time for blood in muscle capillaries (tc) was estimated in six species, spanning two orders of magnitude in body mass and aerobic capacity: horse, steer, dog, goat, fox and agouti. Arterial (CaO2) and mixed venous (CvO2) blood O2 concentrations, blood hemoglobin concentrations ([Hb]) and oxygen uptake rates were measured while the animals ran on a treadmill at a speed that elicited the maximal oxygen consumption rate (VO2max) from each animal. Blood flow to the muscles (Qm) was assumed to be 85% of cardiac output, which was calculated using the Fick relationship.

Differences in blood flow to uterine segments and placentae in relation to sex, intrauterine location and side in pregnant rats.

The effects of location within the left or right uterine horn, position within each uterine horn, and fetal sex on fetal bodymass, blood flow to individual uterine segments associated with fetuses, and blood flow to the maternal portion of the placenta were investigated in rats. Sprague-Dawley rats were anaesthetized on day 5, 10, 15, 20, 21 or 22 of pregnancy, and radioactive microspheres with diameters of 15 mm were injected via a left ventricular cannula to measure blood flow to tissues. Tissues were weighed wet, and the rate of blood flow, corrected for wet mass (ml min-1 g-1 tissue), was calculated.

Human immunodeficiency virus type 1 Tat activity in human neuronal cells: uptake and trans-activation.

Neurological dysfunction in AIDS occurs in the absence of productive infection of neurons, and may involve modulation of neuronal cell function by viral or cellular products released from surrounding infected cells. The human immunodeficiency virus type 1 (HIV-1) trans-activator protein Tat may be one such factor, as it can act as a neurotoxin, induces marked morphological changes in neurons and astrocytes in primary embryonic rodent brain cultures, and is released by certain HIV-1-infected cells. In addition, Tat can alter expression of cellular genes in several non-neuronal cell types.

Nonglucose substrates increase glycogen synthesis in vivo in dog heart.

The effects of circulating nonglucose substrates on insulin-stimulated cardiac glycogen synthesis were studied in the dog heart in vivo using 13C-nuclear magnetic resonance (-NMR) and arteriovenous difference techniques. [1-13C]glycogen was monitored in hearts during an intravenous infusion of 20 mU/min insulin and glucose while [1-13C]glucose (10 mg/min) was infused into the left anterior descending coronary artery. When 1 mmol/min of lactate, pyruvate, or beta-hydroxybutyrate was added to the venous infusion, the measured rate of glycogen synthesis was increased, on average, sixfold.

A double-blind placebo-controlled trial of single-dose intravaginal versus single-dose oral metronidazole in the treatment of trichomonal vaginitis.

Since metronidazole is a mutagen in vitro, there is concern about the widespread systemic use of this drug in women with trichomoniasis, particularly those who are pregnant. A randomized, double-blind, placebo-controlled trial compared a single 2-g intravaginal dose of metronidazole cream with a single 2-g oral dose of metronidazole in patients with a culture positive for Trichomonas organisms. Of the 302 preenrollment cultures completed, 94 (31%) were positive.

Cerebral and spinal cord blood flow dynamics during high sustained +Gz.

This study had two purposes. First, the use of Transonic flowprobes placed on the common carotid and internal carotid arteries of seven male baboons was evaluated for measuring cerebral blood flow (BF) during +Gz stress. The approach was to compare BF's obtained with these flowprobes to microsphere measurements of total cerebral BF.

Cellular latency in HIV-1 infection.

There are multiple levels of transcriptional regulation that a cell can bring to bear on either native cellular genes or integrated proviral genes. One such level of regulation is inducible sequence-specific transcriptional factors, such as NF-kappa B, which have been extensively investigated with respect to the HIV-1 LTR. This level of control can be modified by organization of the integrated HIV-1 provirus into higher order chromatin structures such as nucleosomes and chromatin domains.

Potent inhibition of human immunodeficiency virus type 1 replication by an intracellular anti-Rev single-chain antibody.

Human immunodeficiency virus type 1 (HIV-1) has a complex life cycle, which has made it a difficult target for conventional therapeutic modalities. A single-chain antibody moiety, directed against the HIV-1 regulatory protein Rev, which rescues unspliced viral RNA from the nucleus of infected cells, has now been developed. This anti-Rev single-chain construct (SFv) consists of both light and heavy chain variable regions of anti-Rev monoclonal antibody, which, when expressed intracellularly within human cells, potently inhibits HIV-1 replication.