Strength Training with Blood Flow Restriction Diminishes Myostatin Gene Expression

LAURENTINO, G. C., C. UGRINOWITSCH, H. ROSCHEL, M. S. AOKI, A. G. SOARES, M. NEVES JR, A. Y. AIHARA, A. DA ROCHA CORREA FERNANDES, and V. TRICOLI. Strength Training with Blood Flow Restriction Diminishes Myostatin Gene Expression. Med. Sci. Sports Exerc., Vol. 44, No. 3, pp. 406-412, 2012. Purpose: The aim of the study was to determine whether the similar muscle strength and hypertrophy responses observed after either low-intensity resistance exercise associated with moderate blood flow restriction or high-intensity resistance exercise are associated with similar changes in messenger RNA (mRNA) expression of selected genes involved in myostatin (MSTN) signaling. Methods: Twenty-nine physically active male subjects were divided into three groups: low-intensity (20% one-repetition maximum (1RM)) resistance training (LI) (n = 10), low-intensity resistance exercise associated with moderate blood flow restriction (LIR) (n = 10), and high-intensity (80% 1RM) resistance exercise (HI) (n = 9). All of the groups underwent an 8-wk training program. Maximal dynamic knee extension strength (1RM), quadriceps cross-sectional area (CSA), MSTN, follistatin-like related genes (follistatin (FLST), follistatin-like 3 (FLST-3)), activin IIb, growth and differentiation factor-associated serum protein 1 (GASP-1), and MAD-related protein (SMAD-7) mRNA gene expression were assessed before and after training. Results: Knee extension 1RM significantly increased in all groups (LI = 20.7%, LIR = 40.1%, and HI = 36.2%). CSA increased in both the LIR and HI groups (6.3% and 6.1%, respectively). MSTN mRNA expression decreased in the LIR and HI groups (45% and 41%, respectively). There were no significant changes in activin IIb (P > 0.05). FLST and FLST-3 mRNA expression increased in all groups from pre- to posttest (P < 0.001). FLST-3 expression was significantly greater in the HI when compared with the LIR and LI groups at posttest (P = 0.024 and P = 0.018, respectively). GASP-1 and SMAD-7 gene expression significantly increased in both the LIR and HI groups. Conclusions: We concluded that LIR was able to induce gains in 1RM and quadriceps CSA similar to those observed after traditional HI. These responses may be related to the concomitant decrease in MSTN and increase in FLST isoforms, GASP-1, and SMAD-7 mRNA gene expression.

Decompressive craniectomy and cerebral blood flow regulation in head injured patients: A case studied by perfusion CT

Previous studies have reported increased cerebral blood flow (CBF) velocity after decompressive craniectomy in traumatic brain injury (TBI) patients. A 27-year-old man presented with clinical and tomographic signs of cerebral herniation secondary to TBI. Prior to decompressive craniectomy, hemodynamic study by perfusion computed tomography (CT) indicated diffuse cerebral hyperperfusion. Following surgical decompression, the patient recovered neurologically and perfusion CT disclosed a decrease in the intensity of cerebral perfusion. The patient's blood pressure levels were similar at both pre- and postoperative perfusion CT examinations. This finding provides indirect evidence that decompressive craniectomy may improve mechanisms of CBF regulation in TBI, providing pathophysiological insights in the cerebral hemodynamics of TBI patients. This is the first report analyzing the hemodynamic changes through perfusion CT (PCT) in a patient with decompressive craniotomy due to TBI. (C) 2012 Elsevier Masson SAS. All rights reserved.

Abnormal resting state corticolimbic blood flow in depressed unmedicated patients with major depression: A 15O-H2O PET study

We investigated the differences in the resting state corticolimbic blood flow between 20 unmedicated depressed patients and 21 healthy comparisons. Resting state cerebral blood flow (CBF) was measured with H215O PET. Anatomical MRI scans were performed on an Elscint 1.9 T Prestige system for PET-MRI coregistration. Significant changes in cerebral blood flow indicating neural activity were detected using an ROI-free image subtraction strategy. In addition, the resting blood flow in patients was correlated with the severity of depression as measured by HAM-D scores. Depressed patients showed decreases in blood flow in right anterior cingulate (Brodmann areas 24 and 32) and increased blood flow in left and right posterior cingulate (Brodmann areas 23, 29, 30), left parahippocampal gyrus (Brodmann area 36), and right caudate compared with healthy volunteers. The severity of depression was inversely correlated with the left middle and inferior frontal gyri (Brodmann areas 9 and 47) and right medial frontal gyrus (Brodmann area 10) and right anterior cingulate (Brodmann areas 24, 32) blood flow, and directly correlated with the right thalamus blood flow. These findings support previous reports of abnormalities in the resting state blood flow in the limbic-frontal structures in depressed patients compared to healthy volunteers. Hum Brain Mapp, 2012. (C) 2011 Wiley Periodicals, Inc.

Metformin, but not glimepiride, improves carotid artery diameter and blood flow in patients with type 2 diabetes mellitus

OBJECTIVE: To compare the effects of glimepiride and metformin on vascular reactivity, hemostatic factors and glucose and lipid profiles in patients with type 2 diabetes. METHODS: A prospective study was performed in 16 uncontrolled patients with diabetes previously treated with dietary intervention. The participants were randomized into metformin or glimepiride therapy groups. After four months, the patients were crossed over with no washout period to the alternative treatment for an additional four-month period on similar dosage schedules. The following variables were assessed before and after four months of each treatment: 1) fasting glycemia, insulin, catecholamines, lipid profiles and HbA(1) levels; 2) t-PA and PAI-1 (antigen and activity), platelet aggregation and fibrinogen and plasminogen levels; and 3) the flow indices of the carotid and brachial arteries. In addition, at the end of each period, a 12-hour metabolic profile was obtained after fasting and every 2 hours thereafter. RESULTS: Both therapies resulted in similar decreases in fasting glucose, triglyceride and norepinephrine levels, and they increased the fibrinolytic factor plasminogen but decreased t-PA activity. Metformin caused lower insulin and pro-insulin levels and higher glucagon levels and increased systolic carotid diameter and blood flow. Neither metformin nor glimepiride affected endothelial-dependent or endothelial-independent vasodilation of the brachial artery. CONCLUSIONS: Glimepiride and metformin were effective in improving glucose and lipid profiles and norepinephrine levels. Metformin afforded more protection against macrovascular diabetes complications, increased systolic carotid artery diameter and total and systolic blood flow, and decreased insulin levels. As both therapies increased plasminogen levels but reduced t-PA activity, a coagulation process was likely still ongoing.

Fetal venous Doppler in pregnancies with placental dysfunction and correlation with pH at birth

Objectives: To determine the correlation between ph at birth and venous Doppler parameters in pregnancies with placental dysfunction. Methods: This was a prospective cohort study of 58 pregnancies with the diagnosis of placental dysfunction between 26 and 34 weeks of gestation. Inclusion criteria were singleton pregnancies, abnormal umbilical artery (UA) Doppler, fetal growth restriction diagnosed by estimated fetal weight <10th centile for gestational age, intact membranes, and absence of fetal congenital abnormalities. The Doppler measurements were the following: UA pulsatility index (PI), ductus venosus (DV) pulsatility index for veins (PIV), intra-abdominal umbilical vein (UV) time-averaged maximum velocity (TAMxV) and blood flow and left portal vein (LPV) time-averaged maximum velocity (TAMxV) and blood flow. All Doppler parameters were transformed into z-scores (SD values from the mean) according to normative references. Results: The UA pH at birth showed a negative significant correlation with the DV-PIV (p = 0.004) and the DV-PIV z-score (p = 0.004), while LPV TAMxV (p = 0.004), LPV TAMxV z-score (p = 0.002), LPV blood flow (p = 0.01), LPV blood flow normalized (p = 0.04) and UV blood flow (p = 0.04) positively correlated with pH at birth. Multiple regression analysis was performed and the DV-PIV z-score was the variable that independently correlated with pH at birth (p = 0.002). Conclusions: the present results suggest that changes in fetal venous blood flow, mainly DV and LPV are useful in the management of cases with early onset placental insufficiency and that venous Doppler parameters correlate with pH at birth.

Unilateral ablation of follicles >= 4 mm leads to compensatory follicle response from the contralateral ovary in heifers

In each of two experiments, heifers were assigned to a control group and a unilaterally ablated (UA) group (n = 6/group). In the UA group, follicles >= 4 mm in the left ovary were ablated by transvaginal ultrasound-guided technique at Hour 0 (8:00 AM) on the day of ovulation. Follicles in the CL-bearing right ovary remained intact. In Experiment 1, ablations continued until the next ovulation, and new follicles emerged in the right ovary in 9 of 14 (64%) waves. The number of follicles/wave (combined, 6.4 +/- 0.4) did not differ between groups. In Experiment 2, follicles were counted at Hours 0, 4, 8, 12, and 24; the resistance index (RI) for blood flow in the ovarian pedicle was determined at Hours 0 and 12; and blood samples were collected every hour from Hours 0 to 12 and Hour 24. An increase (P < 0.05) in the number of follicles in the follicle-intact ovary began at Hour 4 with complete compensation by Hour 24. Concentrations of FSH did not change between Hours 0 and 24 in the UA group but decreased (P < 0.05) in the controls by Hour 7. At Hour 12, RI to the right ovary approached being lower (P < 0.06) in the UA group than in the control group. Results indicated that unilateral ablation of follicles >= 4 mm led to compensatory follicle response in the follicle-intact ovary, and initially circulatory FSH concentrations were maintained and blood flow to the follicle-intact ovary increased. (c) 2012 Elsevier Inc. All rights reserved.

Previous Exposure to Cigarette Smoke Aggravates Experimental Cyclosporine-Induced Nephrotoxicity

Background/Aims: The effects of cigarette smoke (CS) on cyclosporine (CsA)-induced nephrotoxicity are poorly studied. This study aims to assess the effects of previous exposure to CS on CsA nephrotoxicity. Methods: Rats were either exposed to CS or sham (S) procedures for 10 min twice a day for 20 weeks. From the 16th to the 20th week, they received a low-salt diet. Beginning with the 17th week, they were given 2.5 mg/day CsA or vehicle (VH) for 3 weeks. The final groups were VH/CS, CsA/CS, VH/S, and CsA/S. On day 141, glomerular filtration rate (GFR), renal blood flow (RBF), renal vascular resistance (RVR), tubulointerstitial fibrosis, and CsA blood levels were measured and immunohistochemistry was analyzed for renal alpha-smooth muscle actin (SMA), nitrotyrosine, and vimentin. Results: CsA decrease in GFR was enhanced by CS exposure. CsA associated with CS induced higher periglomerular alpha-SMA and renal nitrotyrosine expression. CsA decreased RBF, but increased RVR, tubulointerstitial fibrosis, and alpha-SMA and renal vimentin expression. These changes and the CsA blood levels were not affected by CS exposure. Conclusion: CS aggravated the CsA-induced impairment of GFR and CS associated with CsA caused the development of periglomerular structural lesions and oxidative stress in a rat model of CsA nephrotoxicity. Copyright (C) 2012 S. Karger AG, Basel

Exercise training improves neurovascular control and functional capacity in heart failure patients regardless of age

Background: Exercise training is a non-pharmacological strategy for treatment of heart failure. Exercise training improves functional capacity and quality of life in patients. Moreover, exercise training reduces muscle sympathetic nerve activity (MSNA) and peripheral vasoconstriction. However, most of these studies have been conducted in middle-aged patients. Thus, the effects of exercise training in older patients are much less understood. The present study was undertaken to investigate whether exercise training improves functional capacity, muscular sympathetic activation and muscular blood flow in older heart failure patients, as it does in middle-aged heart failure patients. Design: Fifty-two consecutive outpatients with heart failure from the database of the Unit of Cardiovascular Rehabilitation and Physiology Exercise were divided by age (middle-aged, defined as 45-59 years, and older, defined as 60-75 years) and exercise status (trained and untrained). Methods: MSNA was recorded directly from the peroneal nerve using the microneurography technique. Forearm Blood Flow (FBF) was measured by venous occlusion plethysmography. Functional capacity was evaluated by cardiopulmonary exercise test. Results: Exercise training significantly and similarly increased FBF and peak VO2 in middle-aged and older heart failure patients. In addition, exercise training significantly and similarly reduced MSNA and forearm vascular resistance in these patients. No significant changes were found in untrained patients. Conclusion: Exercise training improves neurovascular control and functional capacity in heart failure patients regardless of age.

Mechanisms of blunted muscle vasodilation during peripheral chemoreceptor stimulation in heart failure patients

We described recently that systemic hypoxia provokes vasoconstriction in heart failure (HF) patients. We hypothesized that either the exaggerated muscle sympathetic nerve activity and/or endothelial dysfunction mediate the blunted vasodilatation during hypoxia in HF patients. Twenty-seven HF patients and 23 age-matched controls were studied. Muscle sympathetic nerve activity was assessed by microneurography and forearm blood flow (FBF) by venous occlusion plethysmography. Peripheral chemoreflex control was evaluated through the inhaling of a hypoxic gas mixture (10% O-2 and 90% N-2). Basal muscle sympathetic nerve activity was greater and basal FBF was lower in HF patients versus controls. During hypoxia, muscle sympathetic nerve activity responses were greater in HF patients, and forearm vasodilatation in HF was blunted versus controls. Phentolamine increased FBF responses in both groups, but the increase was lower in HF patients. Phentolamine and N-G-monomethyl-L-arginine infusion did not change FBF responses in HF but markedly blunted the vasodilatation in controls. FBF responses to hypoxia in the presence of vitamin C were unchanged and remained lower in HF patients versus controls. In conclusion, muscle vasoconstriction in response to hypoxia in HF patients is attributed to exaggerated reflex sympathetic nerve activation and blunted endothelial function (NO activity). We were unable to identify a role for oxidative stress in these studies. (Hypertension. 2012; 60: 669-676.) . Online Data Supplement

Atorvastatin Prevents the Downregulation of Aquaporin-2 Receptor After Bilateral Ureteral Obstruction and Protects Renal Function in a Rat Model

OBJECTIVE To assess the effects of atorvastatin (ATORV) on renal function after bilateral ureteral obstruction (BUO), measuring inulin clearance and its effect on renal hemodynamic, filtration, and inflammatory response, as well as the expression of Aquaporin-2 (AQP2) in response to BUO and after the release of BUO. METHODS Adult Munich-Wistar male rats were subjected to BUO for 24 hours and monitored during the following 48 hours. Rats were divided into 5 groups: sham operated (n = 6); sham + ATORV (n = 6); BUO (n = 6); BUO + ATORV (10 mg/kg in drinking water started 2 days before BUO [n = 5]; and BUO + ATORV (10 mg/kg in drinking water started on the day of the release of BUO [n = 5]). We measured blood pressure (BP, mm Hg); inulin clearance (glomerular filtration rate [GFR]; mL/min/100 g); and renal blood flow (RBF, mL/min, by transient-time flowmeter). Inflammatory response was evaluated by histologic analysis of the interstitial area. AQP2 expression was evaluated by electrophoresis and immunoblotting. RESULTS Renal function was preserved by ATORV treatment, even if initiated on the day of obstruction release, as expressed by GFR, measured by inulin clearance. Relative interstitial area was decreased in both BUO + ATORV groups. Urine osmolality was improved in the ATORV-treated groups. AQP2 protein expression decreased in BUO animals and was reverted by ATORV treatment. CONCLUSION ATORV administration significantly prevented and restored impairment in GFR and renal vascular resistance. Furthermore, ATORV also improved urinary concentration by reversing the BUO-induced downregulation of AQP2. These findings have significant clinical implication in treating obstructive nephropathy. UROLOGY 80: 485.e15-485.e20, 2012. (c) 2012 Elsevier Inc.

Activation of central α(2)-adrenoceptors mediates salivary gland vasoconstriction

OBJECTIVE: Peripheral treatment with the cholinergic agonist pilocarpine increases salivary gland blood flow and induces intense salivation that is reduced by the central injection of moxonidine (α(2)-adrenoceptors/imidazoline agonist). In the present study, we investigated the effects of the intracerebroventricular (i.c.v.) injection of pilocarpine alone or combined with moxonidine also injected i.c.v. On submandibular/sublingual gland (SSG) vascular resistance. In addition, the effects of these treatments on arterial pressure, heart rate and on mesenteric and hindlimb vascular resistance were also tested. DESIGN: Male Holtzman rats with stainless steel cannula implanted into lateral ventricle and anaesthetized with urethane+α-chloralose were used. RESULTS: Pilocarpine (500nmol/1μl) injected i.c.v. Reduced SSG vascular resistance and increased arterial pressure, heart rate and mesenteric vascular resistance. Contrary to pilocarpine alone, the combination of moxonidine (20nmol/1μl) and pilocarpine injected i.c.v. Increased SSG vascular resistance, an effect abolished by the pre-treatment with the α(2)-adrenoceptor antagonist yohimbine (320nmol/2μl). The increase in arterial pressure, heart rate and mesenteric resistance was not modified by the combination of moxonidine and pilocarpine i.c.v. CONCLUSION: These results suggest that the activation of central α(2)-adrenoceptors may oppose to the effects of central cholinergic receptor activation in the SSG vascular resistance.