Eight weeks of treatment with mineralocorticoid receptor blockade does not alter vascular function in individuals with and without type 2 diabetes.

Aldosterone has been suggested to be involved in the microvascular complications observed in type 2 diabetes. We aimed to investigate the effect of mineralocorticoid receptor (MR) blockade on endothelial function in individuals with type 2 diabetes compared to healthy controls. We included 12 participants with type 2 diabetes and 14 controls.

The role of T-type calcium channels in elderly human vascular function: A pilot randomized controlled trial.

Endothelial dysfunction develops with age and may precede cardiovascular disease. Animal data suggest that T-type calcium channels play an important role in endothelial function, but data from humans are lacking. This study included 15 healthy, sedentary, elderly males for a double blinded, randomized controlled trial.

Regulation of the microvasculature during small muscle mass exercise in chronic obstructive pulmonary disease vs. chronic heart failure.

Skeletal muscle convective and diffusive oxygen (O) transport are peripheral determinants of exercise capacity in both patients with chronic obstructive pulmonary disease (COPD) and chronic heart failure (CHF). We hypothesised that differences in these peripheral determinants of performance between COPD and CHF patients are revealed during small muscle mass exercise, where the cardiorespiratory limitations to exercise are diminished. Eight patients with moderate to severe COPD, eight patients with CHF (NYHA II), and eight age- and sex-matched controls were studied.

Role of Endothelin-1 Receptors in Limiting Leg Blood Flow and Glucose Uptake During Hyperinsulinemia in Type 2 Diabetes.

Skeletal muscle insulin resistance is a hallmark of individuals with type 2 diabetes mellitus (T2D). In healthy individuals insulin stimulates vasodilation, which is markedly blunted in T2D; however, the mechanism(s) remain incompletely understood. Investigations in rodents indicate augmented endothelin-1 (ET-1) action as a major contributor.

Eight weeks of mineralocorticoid blockade does not improve insulin sensitivity in type 2 diabetes.

Individuals with type 2 diabetes have an increased risk of cardiovascular disease. A correlation between plasma aldosterone and hyperinsulinemia has been demonstrated in vivo, and hyperinsulinemia and insulin resistance are independently associated with the development of cardiovascular complications. We investigated if mineralocorticoid blockade (Eplerenone) improves insulin sensitivity in individuals with type 2 diabetes compared to healthy controls.

Aldosterone Induces Vasoconstriction in Individuals with Type 2 Diabetes: Effect of Acute Antioxidant Administration.

Context: Individuals with type 2 diabetes have an increased risk of endothelial dysfunction and cardiovascular disease. Plasma aldosterone could contribute by reactive oxygen species-dependent mechanisms by inducing a shift in the balance between a vasoconstrictor and vasodilator response to aldosterone.

Objective: We aimed to investigate the acute vascular effects of aldosterone in individuals with type 2 diabetes compared with healthy controls and if infusion of an antioxidant (n-acetylcysteine [NAC]) would alter the vascular response.

Reduced skeletal-muscle perfusion and impaired ATP release during hypoxia and exercise in individuals with type 2 diabetes.

Aims/hypothesis: Plasma ATP is a potent vasodilator and is thought to play a role in the local regulation of blood flow. Type 2 diabetes is associated with reduced tissue perfusion. We aimed to examine whether individuals with type 2 diabetes have reduced plasma ATP concentrations compared with healthy control participants (case-control design).

The effect of two exercise modalities on skeletal muscle capillary ultrastructure in individuals with type 2 diabetes.

Type 2 diabetes is associated with microvascular dysfunction, but little is known about how capillary ultrastructure is affected by exercise training. To investigate the effect of two types of exercise training on skeletal muscle capillary ultrastructure and capillarization in individuals with type 2 diabetes, 21 individuals with type 2 diabetes were allocated (randomized controlled trial) to 11 weeks of aerobic exercise training consisting of either moderate-intensity endurance training (END; n = 10) or low-volume high-intensity interval training (HIIT; n = 11). Skeletal muscle biopsies (m vastus lateralis) were obtained before and after the training intervention.

High-intensity interval, but not endurance, training induces muscle fiber type-specific subsarcolemmal lipid droplet size reduction in type 2 diabetic patients.

This study compared the effects of moderate-intensity endurance training and high-intensity interval training on fiber type-specific subcellular volumetric content and morphology of lipid droplets and mitochondria in skeletal muscles of type 2 diabetic patients. Sixteen sedentary type 2 diabetic patients (57 ± 7 yr old) were randomized to complete 11 wk of either 40-min cycling at 50% peak workload (Endurance, n = 8) or 10 1-min cycling intervals at 95% peak workload separated by 1 min of recovery (High-Intensity Interval, n = 8), three times per week. Assessments for cardiorespiratory fitness, body composition, glycemic control, together with muscle biopsies were performed before and after the intervention.

Methods for the determination of skeletal muscle blood flow: development, strengths and limitations.

Since the first measurements of limb blood flow at rest and during nerve stimulation were conducted in the late 1800s, a number of methods have been developed for the determination of limb and skeletal muscle blood flow in humans. The methods, which have been applied in the study of aspects such as blood flow regulation, oxygen uptake and metabolism, differ in terms of strengths and degree of limitations but most have advantages for specific settings. The purpose of this review is to describe the origin and the basic principles of the methods, important aspects and requirements of the procedures.

Comparative Effectiveness of Low-Volume Time-Efficient Resistance Training Versus Endurance Training in Patients With Heart Failure.

Purpose: Cardiorespiratory fitness is positively related to heart failure (HF) prognosis, but lack of time and low energy are barriers for adherence to exercise. We, therefore, compared the effect of low-volume time-based resistance exercise training (TRE) with aerobic moderate-intensity cycling (AMC) on maximal and submaximal exercise capacity, health-related quality of life, and vascular function.

Methods: Twenty-eight HF patients (New York Heart Association class I-II) performed AMC (n = 14) or TRE (n = 14).

The effect on glycaemic control of low-volume high-intensity interval training versus endurance training in individuals with type 2 diabetes.

Aim: To evaluate whether high-intensity interval training (HIIT) with a lower time commitment can be as effective as endurance training (END) on glycaemic control, physical fitness and body composition in individuals with type 2 diabetes.

Materials And Methods: A total of 29 individuals with type 2 diabetes were allocated to control (CON; no training), END or HIIT groups. Training groups received 3 training sessions per week consisting of either 40 minutes of cycling at 50% of peak workload (END) or 10 1-minute intervals at 95% of peak workload interspersed with 1 minute of active recovery (HIIT).

Effect of 6 wk of high-intensity one-legged cycling on functional sympatholysis and ATP signaling in patients with heart failure.

Breathlessness during daily activities is the primary symptom in patients with heart failure (HF). Poor correlation between the hemodynamic parameters of left ventricular performance and perceived symptoms suggests that other factors, such as skeletal muscle function, play a role in determining exercise capacity. We investigated the effect of 6 wk of high-intensity, one-legged cycling (HIC; 8 × 4 at 90% one-legged cycling max) on 1) the ability to override sympathetic vasoconstriction (arterial infusion of tyramine) during one-legged knee-extensor exercise (KEE), 2) vascular function (arterial infusion of ACh, sodium nitroprusside, tyramine, and ATP), and 3) exercise capacity in HF patients with reduced ejection fraction ( n = 8) compared with healthy individuals ( n = 6).

Effect of endurance versus resistance training on quadriceps muscle dysfunction in COPD: a pilot study.

Introduction: Exercise is an important countermeasure to limb muscle dysfunction in COPD. The two major training modalities in COPD rehabilitation, endurance training (ET) and resistance training (RT), may both be efficient in improving muscle strength, exercise capacity, and health-related quality of life, but the effects on quadriceps muscle characteristics have not been thoroughly described.

Methods: Thirty COPD patients (forced expiratory volume in 1 second: 56% of predicted, standard deviation [SD] 14) were randomized to 8 weeks of ET or RT.

Mechanical compression during repeated sustained isometric muscle contractions and hyperemic recovery in healthy young males.

Background: An elevated intramuscular pressure during a single forearm isometric muscle contraction may restrict muscle hyperemia. However, during repeated isometric exercise, it is unclear to what extent mechanical compression and muscle vasodilatation contribute to the magnitude and time course of beat-to-beat limb hemodynamics, due to alterations in leg vascular conductance (LVC).

Methods: In eight healthy male subjects, the time course of both beat-to-beat leg blood flow (LBF) and LVC in the femoral artery was determined between repeated 10-s isometric thigh muscle contractions and 10-s muscle relaxation (a duty cycle of 20 s) for steady-state 120 s at five target workloads (10, 30, 50, 70, and 90% of maximum voluntary contraction (MVC)).

Left ventricular atrioventricular plane displacement is preserved with lifelong endurance training and is the main determinant of maximal cardiac output.

Age-related decline in cardiac function can be prevented or postponed by lifelong endurance training. However, effects of normal ageing as well as of lifelong endurance exercise on longitudinal and radial contribution to stroke volume are unknown. The aim of this study was to determine resting longitudinal and radial pumping in elderly athletes, sedentary elderly and young sedentary subjects.

Effect of PDE5 inhibition on the modulation of sympathetic α-adrenergic vasoconstriction in contracting skeletal muscle of young and older recreationally active humans.

Aging is associated with an altered regulation of blood flow to contracting skeletal muscle; however, the precise mechanisms remain unclear. We recently demonstrated that inhibition of cGMP-binding phosphodiesterase 5 (PDE5) increased blood flow to contracting skeletal muscle of older but not young human subjects. Here we examined whether this effect of PDE5 inhibition was related to an improved ability to blunt α-adrenergic vasoconstriction (functional sympatholysis) and/or improved efficacy of local vasodilator pathways.

Potentiation of cGMP signaling increases oxygen delivery and oxidative metabolism in contracting skeletal muscle of older but not young humans.

Aging is associated with progressive loss of cardiovascular and skeletal muscle function. The impairment in physical capacity with advancing age could be related to an insufficient peripheral O2 delivery to the exercising muscles. Furthermore, the mechanisms underlying an impaired blood flow regulation remain unresolved.

Blood temperature and perfusion to exercising and non-exercising human limbs.

What is the central question of this study? Temperature-sensitive mechanisms are thought to contribute to blood-flow regulation, but the relationship between exercising and non-exercising limb perfusion and blood temperature is not established. What is the main finding and its importance? The close coupling among perfusion, blood temperature and aerobic metabolism in exercising and non-exercising extremities across different exercise modalities and activity levels and the tight association between limb vasodilatation and increases in plasma ATP suggest that both temperature- and metabolism-sensitive mechanisms are important for the control of human limb perfusion, possibly by activating ATP release from the erythrocytes. Temperature-sensitive mechanisms may contribute to blood-flow regulation, but the influence of temperature on perfusion to exercising and non-exercising human limbs is not established.

Direct effect of incretin hormones on glucose and glycerol metabolism and hemodynamics.

The objective of this study was to assess the insulin-independent effects of incretin hormones on glucose and glycerol metabolism and hemodynamics under euglycemic and hyperglycemic conditions. Young, healthy men (n=10) underwent three trials in a randomized, controlled, crossover study. Each trial consisted of a two-stage (euglycemia and hyperglycemia) pancreatic clamp (using somatostatin to prevent endogenous insulin secretion).

Regulation of the skeletal muscle blood flow in humans.

In humans, skeletal muscle blood flow is regulated by an interaction between several locally formed vasodilators, including NO and prostaglandins. In plasma, ATP is a potent vasodilator that stimulates the formation of NO and prostaglandins and, very importantly, can offset local sympathetic vasoconstriction. Adenosine triphosphate is released into plasma from erythrocytes and endothelial cells, and the plasma concentration increases in both the feed artery and the vein draining the contracting skeletal muscle.

Infusion of ATP increases leg oxygen delivery but not oxygen uptake in the initial phase of intense knee-extensor exercise in humans.

The present study examined whether an increase in leg blood flow and oxygen delivery at the onset of intense exercise would speed the rate of rise in leg oxygen uptake. Nine healthy men (25 ± 1 years old, mean ± SEM) performed one-leg knee-extensor exercise (62 ± 3 W, 86 ± 3% of incremental test peak power) for 4 min during a control setting (CON) and with infusion of ATP into the femoral artery in order to increase blood flow before and during exercise. In the presence of ATP, femoral arterial blood flow and O2 delivery were higher (P < 0.

Exercise training modulates functional sympatholysis and α-adrenergic vasoconstrictor responsiveness in hypertensive and normotensive individuals.

Essential hypertension is linked to an increased sympathetic vasoconstrictor activity and reduced tissue perfusion. We investigated the role of exercise training on functional sympatholysis and postjunctional α-adrenergic responsiveness in individuals with essential hypertension. Leg haemodynamics were measured before and after 8 weeks of aerobic training (3-4 times per week) in eight hypertensive (47 ± 2 years) and eight normotensive untrained individuals (46 ± 1 years) during arterial tyramine infusion, arterial ATP infusion and/or one-legged knee extensions.

Roles of sedentary aging and lifelong physical activity in exchange of glutathione across exercising human skeletal muscle.

Reactive oxygen species (ROS) are important signaling molecules with regulatory functions, and in young and adult organisms, the formation of ROS is increased during skeletal muscle contractions. However, ROS can be deleterious to cells when not sufficiently counterbalanced by the antioxidant system. Aging is associated with accumulation of oxidative damage to lipids, DNA, and proteins.