Ai-Lun Yang

Anti-apoptotic and pro-survival effects of exercise training on hypertensive hearts

BACKGROUND Activated cardiac apoptosis was found in hearts from hypertensive animals, but little information regarding the effects of exercise training on cardiac apoptosis in hypertension is available. The purpose of this study was to evaluate the anti-apoptotic and pro-survival effects of exercise training on hypertensive hearts. METHODS 28 spontaneously hypertensive rats were divided into sedentary group (SHR) or underwent running exercise on treadmill for 1 h/day, 5 sessions/wk, for 12 wk (SHR-EX). Fourteen age-matched Wistar Kyoto rats served as a sedentary normotensive group (WKY). After exercise training or sedentary status, the excised hearts were measured by hemotoxylin and eosin staining, terminal deoxynucleotidyl transferase dUTP-mediated nick-end labeling (TUNEL) assay, and Western blotting. RESULTS Fewer TUNEL-positive apoptotic cells were in SHR-EX groups than those in SHR. Protein levels of Fas ligand, Fas death receptor, tumor necrosis factor (TNF)-α, TNF receptor 1, Fas-associated death domain (FADD), activated caspase-8, and activated caspase-3 (Fas-dependent apoptotic pathways), as well as Bid, t-Bid, Bad, p-Bad, Bak, cytochrome c, activated caspase 9, and activated caspase-3 (mitochondria-dependent apoptotic pathways) were decreased in the SHR-EX group compared with the SHR group. Protein levels of IGF-1, IGF-1R, p-PI3K, p-Akt, p-Bad, and Bcl2 (cardiac pro-survival pathway) become more activated in SHR-EX groups than SHR and WKY. CONCLUSIONS Exercise training prevented hypertension-enhanced cardiac Fas-dependent and mitochondria-dependent apoptotic pathways and enhanced cardiac pro-survival pathway in rat models. Our findings demonstrate new therapeutic effects of exercise training on hypertensive hearts for preventing apoptosis and enhancing survival.

Chronic exercise reduces adhesion molecules/iNOS expression and partially reverses vascular responsiveness in hypercholesterolemic rabbit aortae

To investigate exercise effects on the vascular function in hypercholesterolemia, male New Zealand White rabbits were divided into four groups; i.e. the normal diet control, the high cholesterol diet control, normal diet with exercise, and high cholesterol diet with exercise. High cholesterol diet groups were fed 2% cholesterol rabbit chow for 8 weeks. Animals of exercise groups ran on a treadmill at 0.88 km/h for 10-60 min/day, 5 day/week, and 8 weeks in total. Thoracic aortae were, then, isolated for functional and immunohistochemical analysis. We found that in rabbit aortae, (1). high cholesterol diet feeding caused lipid deposition and intimal thickening, induced expression of P-selectin, VCAM-1, MCP-1 and iNOS, and impaired acetylcholine (ACh)-evoked vasorelaxation; (2). exercise significantly reduced the protein expression of adhesion molecules/iNOS, and the intimal thickness in hypercholesterolemia; (3). chronic exercise enhanced ACh-evoked vasorelaxation in normal rabbits, but it only significantly improved vascular responses to the high dose (10(-6) M) of ACh in hypercholesterolemic rabbits; (4). both exercise and diet effects on vascular responses were mediated by altering the release of NO and endothelium-derived hyperpolarization factor. We conclude that exercise training decreases the expression of adhesion molecules and iNOS, and ameliorates the severe vascular dysfunction induced by high cholesterol feeding.

Cardiac Fas-dependent and mitochondria-dependent apoptosis in ovariectomized rats

BACKGROUND Very limited information has been published regarding cardiac apoptosis in menopausal women or in those after bilateral oophorectomy. The purpose of this study was to evaluate whether cardiac Fas-dependent (type I) and mitochondria-dependent (type II) apoptotic pathways are activated in ovariectomized rats. METHODS Thirty-two female Wistar rats at 6-7 months of age were randomly divided into sham-operated group (Sham) and bilateral ovariectomized group (OVX). Two months after the operation, the cardiac characteristics, myocardial architecture, and two major apoptotic pathways in the excised left ventricle from rats were measured by histopathological analysis, Western blotting and reverse transcription polymerase chain reaction (RT-PCR), and positive TUNEL assays. RESULTS The whole heart weight, the left ventricular weight, the ratios of whole heart weight to tibia length, and the ratios of left ventricle to tibia length were significantly increased in OVX relative to Sham. Abnormal myocardial architecture, enlarged interstitial spaces, more minor cardiac fibrosis, and more cardiac TUNEL-positive apoptotic cells were observed in OVX. The key components of Fas-dependent apoptosis (TNF-alpha, Fas ligand, Fas death receptors, Fas-associated death domain (FADD), activated caspase 8, and activated caspase 3) and key components of mitochondria-dependent apoptosis (Bad, Bax, Bax-to-Bcl2 ratio, cytosolic cytochrome c, activated caspase 9, and activated caspase 3) were significantly increased in OVX hearts. CONCLUSIONS The absence of female ovaries will activate the cardiac Fas-dependent and mitochondria-dependent apoptotic pathways, which might provide one of possible mechanism for developing heart failure in post-menopause women.

Chronic Exercise Increases Both Inducible and Endothelial Nitric Oxide Synthase Gene Expression in Endothelial Cells of Rat Aorta

Chronic exercise upregulates endothelial nitric oxide synthase (eNOS) gene expression. Whether the expression of inducible nitric oxide synthase (iNOS) is affected by exercise is unknown. We therefore investigated the effects of chronic exercise on iNOS and eNOS expression in isolated rat aortic endothelial and smooth muscle cells separately. Five-week-old male Wistar rats were randomly divided into control and exercise groups. After 10 weeks of running training, animals were sacrificed under ether anesthesia. The standard curve quantitative competitive reverse transcriptase-polymerase chain reaction method was used to quantify NOS mRNA expression in isolated endothelial/smooth muscle cells. To evaluate the functional role of iNOS, we examined phenylephrine-induced vascular responses with or without pretreatment with aminoguanidine. We found that (1) expression of iNOS and eNOS mRNA in endothelial cells was increased by chronic exercise and (2) chronic exercise blunted phenylephrine-induced vascular responses, probably by increasing NO release via iNOS. Our results show that chronic exercise increases both iNOS and eNOS gene expression in endothelium. These alterations may be partially responsible for the change in vascular response after exercise.

Effects of 17beta-estradiol on cardiac apoptosis in ovariectomized rats

Cardiac apoptosis was found in ovariectomized rats without ischemia. Limited information regarding the protective effects of 17β‐estradiol (E2) on cardiac Fas‐dependent and mitochondria‐dependent apoptotic pathways after post‐menopause or bilateral oophorectomy in women was available.

Enhancement of vasorelaxation in hypertension following high-intensity exercise.

Exercise can ameliorate vascular dysfunction in hypertension, but its underlying mechanism has not been explored thoroughly. We aimed to investigate whether the high-intensity exercise could enhance vasorelaxation mediated by insulin and insulin-like growth factor-1 (IGF-1) in hypertension. Sixteen-week-old spontaneously hypertensive rats were randomly divided into non-exercise sedentary (SHR) and high-intensity exercise (SHR+Ex) groups conducted by treadmill running at a speed of 30 m/ min until exhaustion. Age-matched Wistar-Kyoto rats (WKY) were used as the normotensive control group. Immediately after exercise, the agonist-induced vasorelaxation of aortas was evaluated in organ baths with or without endothelial denudation. Selective inhibitors were used to examine the roles of nitric oxide synthase (NOS) and phosphatidylinositol-3 kinase (PI3K) in the vasorelaxation. By adding superoxide dismutase (SOD), a superoxide scavenger, the role of superoxide production in the vasorelaxation was also clarified. We found that, the high-intensity exercise significantly (P < 0.05) induced higher vasorelaxant responses to insulin and IGF-1 in the SHR+Ex group than that in the SHR group; after endothelial denudation and pre-treatment of the PI3K inhibitor, NOS inhibitor, or SOD, vasorelaxant responses to insulin and IGF-1 became similar among three groups; the protein expression of insulin receptor, IGF-1 receptor, and endothelial NOS (eNOS) was significantly (P < 0.05) increased in the SHR+Ex group compared with the SHR group;] the relaxation to sodium nitroprusside, a NO donor, was not different among three groups. Our findings suggested that the high-intensity exercise ameliorated the insulin- and IGF-1-mediated vasorelaxation through the endothelium-dependent pathway, which was associated with the reduced level of superoxide production.

Altered insulin-mediated and insulin-like growth factor-1-mediated vasorelaxation in aortas of obese Zucker rats

Objective:Insulin and insulin-like growth factor-1 (IGF-1) have vasorelaxant effects in vivo, which is dependent on nitric oxide (NO) production. The aim of this study was to investigate the vasorelaxant responses mediated by insulin and/or IGF-1 in aortas of obese Zucker rats.Methods:The thoracic aortas of eight lean and eight obese Zucker rats (6 months old) were isolated for vasorelaxation analysis. Insulin-induced and IGF-1-induced vasorelaxant responses were evaluated by the isometric tension of aortic rings in the organ bathes. The roles of phosphatidylinositol 3-kinase (PI3K) and nitric oxide synthase (NOS) in vasorelaxant responses were examined by treating selective inhibitors, such as wortmannin (an inhibitor of PI3K) and N ω-nitro-L-arginine methyl ester (L-NAME, a NOS inhibitor). In addition, the vascular responses to sodium nitroprusside (SNP), a direct vasodilator of vascular smooth muscle, were examined.Results:The insulin-induced vasorelaxation in aortas of obese rats was significantly decreased, whereas the IGF-1-induced vasorelaxation was significantly increased, compared with that in lean rats. After the pre-administration of wortmannin or L-NAME, the altered insulin-induced or IGF-1-induced vasorelaxation was abolished. There was no significant difference in the SNP-induced vasorelaxation between lean and obese rats.Conclusion:Our findings suggested that the decreased insulin-mediated vasorelaxation in obese rats appeared to be counteracted by the increased IGF-1-mediated vasorelaxation. Furthermore, the NO-dependent pathway was involved in the altered vasorelaxant responses. However, the SNP-induced vasorelaxation was not changed in obese rats.

Balance in children with attention deficit hyperactivity disorder-combined type.

The balance ability in children with attention deficit hyperactivity disorder-combined type (ADHD-C) has not been fully examined, particularly dynamic sitting balance. Moreover, the findings of some published studies are contradictory. We examined the static and dynamic sitting balance ability in 20 children with ADHD-C (mean age: 9 years 3 months; 18 boys, 2 girls) and 20 age-, sex-, height-, weight-, and IQ-matched healthy and typically developing controls (mean age: 9 years 2 months; 18 boys, 2 girls). The balance subtests of the Movement Assessment Battery for Children (MABC) and the Bruininks-Oseretsky Test of Motor Proficiency (BOTMP) were used to compare the two groups, and a mechanical horseback riding test was recorded using a motion-capture system. Compared with the controls, children with ADHD-C had less-consistent patterns of movement, more deviation of movement area, and less-effective balance strategies during mechanical horseback riding. In addition, their performance on the balance subtests of the MABC and BOTMP were not as well as those of the controls. Our findings suggest that balance ability skill levels in children with ADHD-C were generally not as high as those of the controls in various aspects, including static and dynamic balance.

Aerobic exercise acutely improves insulin‐ and insulin‐like growth factor‐1‐mediated vasorelaxation in hypertensive rats

Limited information is available concerning the effects of aerobic exercise on vasorelaxation in hypertension. The aim of this study was to investigate the effects of a single bout of aerobic exercise on insulin‐ and insulin‐like growth factor‐1 (IGF‐1)‐induced vasorelaxation in hypertensive rats. Four‐month‐old spontaneously hypertensive rats were randomly divided into a sedentary group (SHR) and an exercise group (SHR+Ex) subjected to a single bout of aerobic exercise conducted by treadmill running at 21 m min−1 for 1 h. Age‐matched Wistar–Kyoto rats were used as a normotensive control group (WKY). Insulin‐ and IGF‐1‐induced vasorelaxant responses in the three groups were evaluated by using isolated aortic rings, with or without endothelial denudation, in organ baths. Possible roles of phosphatidylinositol 3‐kinase (PI3K) and nitric oxide synthase (NOS) involved in the NO‐dependent vasorelaxation were examined by adding selective inhibitors. The role of superoxide was also clarified by adding superoxide dismutase (SOD). In addition, the endothelium‐independent vascular responses to sodium nitroprusside (SNP), a NO donor, were examined. The insulin‐ and IGF‐1‐induced vasorelaxation was significantly (P < 0.05) decreased in the SHR group compared with the WKY group. This decreased response in SHR was improved by exercise. These vasorelaxant responses among the three groups became similar after endothelial denudation and pretreatment with the PI3K inhibitor, NOS inhibitor or SOD. Also, no difference among groups was found in the SNP‐induced vasorelaxation. We concluded that a single bout of aerobic exercise acutely improves insulin‐ and IGF‐1‐mediated vasorelaxation in an endothelium‐dependent manner in hypertensive rats.

Lower Exercise Capacity in Children with Asymptomatic Atrial Septal Defect Associated with Circulatory Impairment

The exercise capacity and limitation in children with asymptomatic atrial septal defect (ASD) have not been explored thoroughly. The aim of our study was to examine the influence of asymptomatic ASD on exercise capacity in children. Fifty children with asymptomatic ASD who had undergone medical interventions at least 4 years ago and fifty normal children were recruited in this study. The exercise capacity was assessed by the symptom-limited exercise test through the Bruce treadmill protocol. The pulmonary function was also evaluated by the spirometry. Circulatory and ventilatory impairments were respectively reflected by chronotropic incompetence (CI) and ventilatory limitation as measured by the exercise test and spirometry. Eleven (22%) of children with ASD failed to reach the age-predicted peak heart rate during the exercise test. Also, children with ASD had significantly lower oxygen consumption at anaerobic threshold and peak exercise (P < 0.01). The rate of circulatory impairment was significantly higher in children with ASD (P < 0.01). However, the pulmonary function and ventilatory limitation were comparable between these two groups. Within the ASD group, children with CI had significantly worse peak oxygen consumption than their peers without CI (P < 0.01). Our study examined a larger population sample and confirmed that children with asymptomatic ASD, who had previously undergone medical interventions, had significantly worse exercise capacity than normal children. This difference in exercise capacity was mainly related to circulatory impairment. Our findings support the concerns of exercise limitation in ASD children.