Previous studies have hypothesized that tumor blood flow may be elevated or reduced during exercise, which could impact the microenvironment. However, to date technical limitations precluded measurement of exercise. Using an orthotopic preclinical model prostate cancer, we tested hypotheses exercise tumors would experience 1) diminished vascular resistance, 2) augmented flow, 3) increased numbers perfused vessels, and 4) decreased tissue hypoxia and, furthermore, perfusion associated with...

Evidence indicates that cerebral blood flow is both increased and diminished in astronauts on return to Earth. Data from ground-based animal models simulating the effects of microgravity have shown decrements perfusion are associated with enhanced vasoconstriction structural remodeling arteries. Based these results, purpose this study was test hypothesis 13 d spaceflight [Space Transportation System (STS)-135 shuttle mission] enhances myogenic vasoconstriction, increases medial wall...

Regular physical exercise is considered to be an integral component of cancer care strategies. However, the effect training on tumor microvascular oxygenation, hypoxia, and vascular function, all which can affect microenvironment, remains unknown. Using orthotopic preclinical model prostate cancer, we tested hypotheses that, after training, in tumor, there would enhanced Po2, increased number patent vessels, reduced hypoxia. We also investigated resistance artery contractile properties....

Angiotensin II has been implicated in maladaptive right ventricular (RV) hypertrophy and fibrosis associated with pulmonary hypertension (PH). Natriuretic peptides decrease RV afterload by promoting vasodilation inhibiting vascular remodeling but are degraded neprilysin. We hypothesized that angiotensin receptor blocker neprilysin inhibitor, sacubitril/valsartan (Sac/Val, LCZ696), will attenuate PH improve function targeting both remodeling. was induced rats using the SU5416/hypoxia model...

Although mechanical ventilation is a life-saving intervention in patients suffering from respiratory failure, prolonged often associated with numerous complications including problematic weaning. In contracting skeletal muscle, inadequate oxygen supply can limit oxidative phosphorylation resulting muscular fatigue. However, whether results decreased diaphragmatic blood flow and induces an supply-demand imbalance the diaphragm remains unknown.We tested hypothesis that controlled...

We investigated the effects of different diets on adipose tissue, liver, serum morphology, and biomarkers in rats that voluntarily exercised. Male Sprague-Dawley (∼9-10 wk age) exercised with resistance-loaded voluntary running wheels (EX; loaded 20-60% body mass) or remained sedentary (SED) over 6 wk. EX SED were provided isocaloric amounts either a ketogenic diet (KD; 20.2%-10.3%-69.5% protein-carbohydrate-fat), Western (WD; 15.2%-42.7-42.0%), standard chow (SC; 24.0%-58.0%-18.0%); n =...

Reduced exercise capacity in pulmonary hypertension (PH) significantly impacts quality of life. However, the cause reduced PH remains unclear. The objective this study was to investigate whether intrinsic skeletal muscle changes are causative using preclinical rat models with different severity. induced adult Sprague-Dawley (SD) or Fischer (CDF) rats one dose SU5416 (20 mg/kg) injection, followed by 3 weeks hypoxia and additional 0-4 normoxia exposure. Control s were injected vehicle housed...

With old age, blood flow to the high-oxidative red skeletal muscle is reduced and low-oxidative white elevated during exercise. Changes in number of feed arteries perforating are thought contribute this altered hyperemic response We tested hypothesis that exercise training would ameliorate age-related differences artery structure muscle. Young (6–7 mo old, n = 36) (24 25) male Fischer 344 rats were divided into young sedentary (Sed), Sed, exercise-trained (ET), ET groups, where consisted...

Exercise training induces multiple adaptations within skeletal muscle that may improve local O(2) delivery-utilization matching (i.e., Po(2)mv). We tested the hypothesis increased nitric oxide (NO) function is intrinsic to improved Po(2)mv kinetics from rest contractions after exercise training. Healthy young Sprague-Dawley rats were assigned sedentary (n = 18) or progressive treadmill 10; 5 days/wk, 6-8 wk, final workload of 60 min/day at 35 m/min, -14% grade) groups. was measured via...

We determined the short- and long-term effects of a ketogenic diet (KD) or ketone salt (KS) supplementation on multi-organ oxidative stress mitochondrial markers. For short-term feedings, 4 month-old male rats were provided isocaloric amounts KD (n = 10), standard chow (SC) 10) SC + KS (~1.2 g/day, n 10). 8), 7) for 8 months rotarod tested every 2 months. Blood, brain (whole cortex), liver gastrocnemius muscle harvested from all biochemical analyses. Additionally, mitochondria brain, tissue...

Given the critical role of tumor O2 delivery in patient prognosis and rise preclinical exercise oncology studies, we investigated host tissue blood flow at rest during as well vascular reactivity using a rat prostate cancer model grown two transplantation sites. In male COP/CrCrl rats, (via radiolabeled microspheres) to tumors [R3327-MatLyLu cells injected left flank (ectopic) or ventral (orthotopic)] was measured bout mild-intensity exercise. α-Adrenergic vasoconstriction norepinephrine...

Following exposure to microgravity, there is a reduced ability of astronauts augment peripheral vascular resistance, often resulting in orthostatic hypotension. The purpose this study was test the hypothesis that mesenteric arteries and veins will exhibit diminished vasoconstrictor responses after spaceflight. Mesenteric from female mice flown on Space Transportation System (STS)-131 (n=11), STS-133 (n=6), STS-135 (n=3) shuttle missions respective ground-based control (n=30) were isolated...

Conditions during spaceflight, such as the loss of head-to-foot gravity vector, are thought to potentially alter cerebral blood flow and vascular resistance. The purpose present study was determine effects long-term spaceflight on functional, mechanical, structural properties arteries. Male C57BL/6N mice were flown 30 days in a Bion-M1 biosatellite. Basilar arteries isolated from (SF) ( n = 6), habitat control (HC) vivarium (VC) 16) used for vitro functional mechanical testing histological...

Chronic heart failure (CHF) impairs nitric oxide (NO)-mediated regulation of skeletal muscle O2 delivery-utilization matching such that microvascular oxygenation falls faster (i.e., speeds PO2mv kinetics) during increases in metabolic demand. Conversely, exercise training improves (slows) kinetics following contractions onset healthy young individuals via NO-dependent mechanisms. We tested the hypothesis would improve contracting CHF rats partly improved NO-mediated function. (left...

With advancing age, there is a reduction in exercise tolerance, resulting, part, from perturbed ability to match O 2 delivery uptake within skeletal muscle. In the spinotrapezius muscle (which not recruited during incline treadmill running) of aged rats, we tested hypotheses that training will 1) improve matching uptake, evidenced through improved microvascular Po (Pm ), at rest and throughout contractions transient; 2) enhance endothelium-dependent vasodilation first-order arterioles. Young...

The long interspersed nuclear element-1 (L1) is a retrotransposon that constitutes 17% of the human genome and associated with various diseases aging. Estimates suggest ~100 L1 copies are capable copying pasting into other regions genome. Herein, we examined if skeletal muscle markers affected by aging or an acute bout cycling exercise in humans. Apparently healthy younger (23 ± 3 y, n = 15) older participants (58 8 donated vastus lateralis biopsy before 1 h (PRE) at ~70% heart rate reserve....

Mechanical ventilation (MV) is a life-saving intervention, yet with prolonged MV (i.e., ≥6 h) there are time-dependent reductions in diaphragm blood flow and an impaired hyperemic response of unknown origin. Female Sprague-Dawley rats (4-8 mo, n = 118) were randomized into two groups; spontaneous breathing (SB) 6-h (prolonged) MV. After or SB, vasodilation (flow-induced, endothelium-dependent -independent agonists) constriction (myogenic α-adrenergic) responses measured first-order (1A)...

Testicular function and associated testosterone concentration decline with advancing age, an impaired O 2 supply may contribute, in part, to this reduction. We hypothesized that there would be a reduced microvascular Po (Po m ) the testes from aged rats, vasomotor control isolated resistance arterioles. In addition, given positive effect of exercise on arteriolar function, we further enhanced animals after aerobic training. was measured vivo via phosphorescence quenching young sedentary...

Spaceflight has profound effects on vascular function as a result of weightlessness that may be further compounded by radiation exposure. The purpose the present study was to assess individual and combined hindlimb unloading (HU) (Rad) vasodilator responses in skeletal muscle vasculature. Adult male C57BL/6J mice were randomized one four groups: control (Con), HU (tail suspension for 15 days), Rad (200 cGy (137)Cs), HU-Rad (15-day tail 200 (137)Cs). Endothelium-dependent vasodilation...

Pulmonary hypertension is associated with pronounced exercise intolerance (decreased V ċ O 2 max) that can significantly impact quality of life. The cause in pulmonary remains unclear. Mitochondrial supercomplexes are large respiratory assemblies individual electron transport chain complexes which promote more efficient respiration. In this study, we examined and exercise‐induced changes skeletal muscle protein expression supercomplex assembly. arterial was induced rats the Sugen/Hypoxia...

We sought to determine the effects of long-term voluntary wheel running on markers long interspersed nuclear element-1 (L1) in skeletal muscle, liver, and hippocampus female rats. In addition, cGAS-STING DNA-sensing pathway that results inflammation were interrogated. Female Lewis rats (n = 34) separated into one three groups including a 6-mo-old group serve as young comparator (CTL, n 10), had access for (EX, 12), an age-matched did not (SED, 12). Both SED EX carried out from 6 mo 15 age....

Spinal cord injury (SCI) produces diminished bone perfusion and loss in the paralyzed limbs. Activity-based physical therapy (ABPT) modalities that mobilize and/or reload limbs (e.g., bodyweight-supported treadmill training (BWSTT) passive-isokinetic bicycle training) transiently promote lower-extremity blood flow (BF). However, it remains unknown whether ABPT alter resting-state BF or improve skeletal integrity after SCI.Four-month-old male Sprague-Dawley rats received T 9 laminectomy alone...

Diminished bone perfusion develops in response to disuse and has been proposed as a mechanism underlying loss. Bone blood flow (BF) not investigated within the unique context of severe contusion spinal cord injury (SCI), condition that produces neurogenic loss is precipitated by other physiological consequences central nervous system injury. Herein, 4-mo-old male Sprague-Dawley rats received T9 laminectomy (SHAM) or with SCI (n = 20/group). Time course assessments hindlimb microstructure...