Prolonged Administration of Rudgea viburnoides (Cham.) Benth. Prevents Impairment of Redox Status, Renal Dysfunction, and Cardiovascular Damage in 2K1C-Hypertensive Rats by Inhibiting ACE Activity and NO-GMPC Pathway Activation.

Rudgea viburnoides is widely found in the Brazilian Cerrado, and commonly used in Brazilian folk medicine. In this study, we evaluated the effects of prolonged administration of the aqueous extract from R. viburnoides leaves (AERV) on impaired redox status, renal dysfunction, and cardiovascular damage in 2K1C hypertensive rats, as well as its chemical composition by LC-DAD-MS. Renal hypertension (two kidney, one-clip model) was surgically induced in male Wistar rats and AERV (30, 100 and 300 mg/kg) was administered orally five weeks after surgery for 28 days. Renal function was assessed and urinary electrolytes, pH, and density were measured. Electrocardiography, blood pressure and heart rate were recorded. Cardiac and mesenteric vascular beds were isolated for cardiac morphometry and evaluation of vascular reactivity, and aortic rings were also isolated for measurement of cyclic guanosine monophosphate levels, and the redox status was assessed. Prolonged treatment with AERV preserved urine excretion and electrolyte levels (Na+, K+, Ca2+ and Cl-), reversed electrocardiographic changes, left ventricular hypertrophy and changes in vascular reactivity induced by hypertension, and reduced blood pressure and heart rate. This effect was associated with a positive modulation of tissue redox state, activation of the NO/cGMP pathway, and inhibition of the angiotensin-converting enzyme. Glycosylated iridoids, chlorogenic acids, glycosylated triterpenes, O-glycosylated flavonols, and triterpenoid saponins were annotated. AERV showed no acute toxicity in female Wistar rats. Therefore, AERV treatment reduced the progression of cardiorenal disease in 2K1C hypertensive rats, which can be involved with an important attenuation of oxidative stress, angiotensin-converting enzyme inhibition, and activation of the NO/cGMP pathway.

Vitamin B12 Supplementation and NT-proBNP Levels in COPD Patients: A Secondary Analysis of a Randomized and Controlled Study in Rehabilitation.

PURPOSE: There is evidence of complex interaction between vitamin B12 (vB12) level, hyperhomocysteinemia (HyCy), and natriuretic peptide secretion. Exercise training could also modulate such interaction. In this secondary analysis of a Randomized Clinical Trial performed in a chronic obstructive pulmonary disease (COPD) rehabilitation setting, our primary objective was to investigate the interaction between vB12 supplementation, exercise training, and changes in NT-proBNP levels after 8 weeks of intervention. Secondary objectives were to explore the correlations between acute changes in NT-proBNP levels with (i) acute exercise and (ii) oxygen uptake (V'O2) kinetics during rest-to-exercise transition. METHODS: Thirty-two subjects with COPD were randomized into four groups: Rehabilitation+vB12 (n = 8), Rehabilitation (n = 8), vB12 (n = 8), or Maltodextrin(n = 8). They were evaluated at baseline and after 8 weeks, during resting and immediately after maximal exercise constant work-rate tests (CWTs, Tlim), for NT-proBNP plasmatic levels. RESULTS: After interaction analysis, the supplementation with vB12 significantly changed the time course of NT-proBNP responses during treatment (p = 0.048). However, the final analysis could not support a significant change in NT-proBNP levels owing to high-intensity constant work-rate exercise (p-value > 0.05). There was a statistically significant correlation between V'O2 time constant and ΔNT-proBNP values (Tlim - rest) at baseline (p = 0.049) and 2 months later (p = 0.015), considering all subjects (n = 32). CONCLUSION: We conclude that vB12 supplementation could modulate NT-proBNP secretion. Moreover, possibly, the slower the initial V'O2 adjustments toward a steady-state during rest-to-exercise transitions, the more severe the ventricular chamber volume/pressure stress recruitment, expressed through higher NT-proBNP secretion in subjects with larger V'O2 time constants, despite unchanged final acute exercise-induced neurohormone secretion.

Addition of vitamin B12 to exercise training improves cycle ergometer endurance in advanced COPD patients: A randomized and controlled study.

Vitamin B12 is essential in the homocysteine, mitochondrial, muscle and hematopoietic metabolisms, and its effects on exercise tolerance and kinetics adjustments of oxygen consumption (V'O2p) in rest-to-exercise transition in COPD patients are unknown. This randomized, double-blind, controlled study aimed to verify a possible interaction between vitamin B12 supplementation and these outcomes. After recruiting 69 patients, 35 subjects with moderate-to-severe COPD were eligible and 32 patients concluded the study, divided into four groups (n = 8 for each group): 1. rehabilitation group; 2. rehabilitation plus B12 group; 3. B12 group; and 4. placebo group. The primary endpoint was cycle ergometry endurance before and after 8 weeks and the secondary endpoints were oxygen uptake kinetics parameters (time constant). The prevalence of vitamin B12 deficiency was high (34.4%) and there was a statistically significant interaction (p < 0.05), favoring a global effect of supplementation on exercise tolerance in the supplemented groups compared to the non-supplemented groups, even after adjusting for confounding variables (p < 0.05). The same was not found for the kinetics adjustment variables (τV'O2p and MRTV'O2p, p > 0.05 for both). Supplementation with vitamin B12 appears to lead to discrete positive effects on exercise tolerance in groups of subjects with more advanced COPD and further studies are needed to establish indications for long-term supplementation.

Reliability of peak O2 uptake and O2 uptake kinetics in step exercise tests in healthy subjects.

To date little is known about the reliability of peak oxygen consumption (V˙O2PEAK) in incremental metronome paced step tests (IST) and the reliability of on-kinetics V˙O2 has never been studied. We aimed to study the reliability of both tests. Eleven healthy subjects performed two ISTs until exhaustion. On two different days two duplicate 4min constant metronome paced step tests (CST) were performed. V˙O2PEAK, mean response time (MRT) and phase II time constant (τ) were tested for reproducibility using the paired t-tests, in addition to the limits of agreement (LOA) and within subject coefficient of variation (COV). With a 95% LOA of 0.38 to 0.26Lmin(-1), -8.7 to 9.1s and -9.9 to 10.5s they exhibit a COV of 3%, 4.5% and 6.9% for V˙O2PEAK, MRT and τ respectively. ST are sufficiently reliable for maximal and submaximal aerobic power assessments in healthy subjects and new studies of oxygen uptake kinetics in selected patient groups are warranted.