ABSTRACT
Pulmonary arterial hypertension (PAH) is characterized by exercise intolerance. Muscle blood flow may be reduced during exercise in PAH; however, this has not been directly measured. Therefore, we investigated blood flow during exercise in a rat model of monocrotaline (MCT)-induced pulmonary hypertension (PH). Male Sprague-Dawley rats (â¼200 g) were injected with 60 mg/kg MCT (MCT, n = 23) and vehicle control (saline; CON, n = 16). Maximal rate of oxygen consumption (VÌo2max) and voluntary running were measured before PH induction. Right ventricle (RV) morphology and function were assessed via echocardiography and invasive hemodynamic measures. Treadmill running at 50% VÌo2max was performed by a subgroup of rats (MCT, n = 8; CON, n = 7). Injection of fluorescent microspheres determined muscle blood flow via photo spectroscopy. MCT demonstrated a severe phenotype via RV hypertrophy (Fulton index, 0.61 vs. 0.31; P < 0.001), high RV systolic pressure (51.5 vs. 22.4 mmHg; P < 0.001), and lower VÌo2max (53.2 vs. 71.8 mL·min-1·kg-1; P < 0.0001) compared with CON. Two-way ANOVA revealed exercising skeletal muscle blood flow relative to power output was reduced in MCT compared with CON (P < 0.001), and plasma lactate was increased in MCT (10.8 vs. 4.5 mmol/L; P = 0.002). Significant relationships between skeletal blood flow and blood lactate during exercise were observed for individual muscles (r = -0.58 to -0.74; P < 0.05). No differences in capillarization were identified. Skeletal muscle blood flow is significantly reduced in experimental PH. Reduced blood flow during exercise may be, at least in part, consequent to reduced exercise intensity in PH. This adds further evidence of peripheral muscle dysfunction and exercise intolerance in PAH.
Subject(s)
Hypertension, Pulmonary , Animals , Male , Rats , Disease Models, Animal , Hemodynamics , Hypertension, Pulmonary/chemically induced , Lactates , Monocrotaline/toxicity , Muscle, Skeletal , Pulmonary Artery , Rats, Sprague-DawleyABSTRACT
We have recently demonstrated that dietary nitrate, a source of nitric oxide (NO) via the nitrate â nitrite â NO enterosalivary pathway, can improve muscle contractility in healthy older men and women. Nitrate ingestion has also been shown to reduce blood pressure in some, but not all, studies of older individuals. However, the optimal dose for eliciting these beneficial effects is unknown. A pilot randomized, double-blind, placebo-controlled crossover study was therefore performed to determine the effects of ingesting 3.3 mL/kg of concentrated beetroot juice containing 0, 200, or 400 µmol/kg of nitrate in 9 healthy older subjects (mean age 70 ± 1 years). Maximal knee extensor power (Pmax) and speed (Vmax) were measured ~2.5 hours after nitrate ingestion using isokinetic dynamometry. Blood pressure was monitored periodically throughout each study. Pmax (in W/kg) was higher (p < .05) after the lower dose (3.9 ± 0.4) compared to the placebo (3.7 ± 0.4) or higher dose (3.7 ± 0.4). Vmax (in rad/s) also tended to be higher (p = .08) after the lower dose (11.9 ± 0.7) compared to the placebo (10.8 ± 0.8) or higher dose (11.2 ± 0.8). Eight out of 9 subjects achieved a higher Pmax and Vmax after the lower versus the higher dose. These dose-related changes in muscle contractility generally paralleled changes in breath NO levels. No significant changes were found in systolic, diastolic, or mean arterial blood pressure. A lower dose of nitrate increases muscle speed and power in healthy older individuals, but these improvements are lost at a higher dose. Blood pressure, on the other hand, is not reduced even with a higher dose.
Subject(s)
Beta vulgaris , Dose-Response Relationship, Drug , Muscle Contraction/drug effects , Nitrates/pharmacology , Nitric Oxide , Aged , Blood Pressure/drug effects , Breath Tests/methods , Dietary Supplements , Double-Blind Method , Female , Fruit and Vegetable Juices , Healthy Volunteers , Humans , Male , Monitoring, Physiologic/methods , Nitric Oxide/analysis , Nitric Oxide/metabolism , Outcome Assessment, Health Care , Phytochemicals/pharmacology , Pilot ProjectsABSTRACT
BACKGROUND: Aging results in reductions in maximal muscular strength, speed, and power, which often lead to functional limitations highly predictive of disability, institutionalization, and mortality in elderly adults. This may be partially due to reduced nitric oxide (NO) bioavailability. We, therefore, hypothesized that dietary nitrate (NO3-), a source of NO via the NO3- â nitrite (NO2-) â NO enterosalivary pathway, could increase muscle contractile function in older subjects. METHODS: Twelve healthy older (age 71 ± 5 years) men and women were studied using a randomized, double-blind, placebo-controlled, crossover design. After fasting overnight, subjects were tested 2 hours after ingesting beetroot juice containing or devoid of 13.4 ± 1.6 mmol NO3-. Plasma NO3- and NO2- and breath NO were measured periodically, and muscle function was determined using isokinetic dynamometry. RESULTS: N O 3 - ingestion increased (p < .001) plasma NO3-, plasma NO2-, and breath NO by 1,051% ± 433%, 138% ± 149%, and 111% ± 115%, respectively. Maximal velocity of knee extension increased (p < .01) by 10.9% ± 12.1%. Maximal knee extensor power increased (p < .05) by 4.4% ± 7.8%. CONCLUSIONS: Acute dietary NO3- intake improves maximal knee extensor angular velocity and power in older individuals. These findings may have important implications for this population, in whom diminished muscle function can lead to functional limitations, dependence, and even premature death.
