Effects of Resistance Training Intensity on Heart Rate Variability at Rest and in Response to Orthostasis in Middle-Aged and Older Adults.

OBJECTIVE: Aging and deficits related to decreased physical activity can lead to higher risks of autonomic nervous system (ANS) dysfunction. The aim of this study was to evaluate the effects of 24 weeks of resistance training (RT) at various intensities on hemodynamics as well as heart rate variability (HRV) at rest and in response to orthostatic tests in middle-aged and older adults. METHODS: Forty adults were randomized into three groups: high-intensity (HEX) (80% 1-RM) (11 female, 4 male; 60 ± 4 years); low-moderate-intensity (LEX) (50% 1-RM) (nine female, four male; 61 ± 5 years); and a control group (CON) (eight female, four male; 60 ± 4 years). The RT program consisted of nine exercises, with two sets performed of each exercise two times per week for 24 weeks. Data collected included 1-RM, heart rate, and blood pressure and HRV at rest and in response to orthostasis. RESULTS: Both the HEX (42-94%) and LEX (31.3-51.7%) groups showed increases in 1-RM (p < 0.01). The HEX group showed decreases in resting heart rate (-4.0%), diastolic blood pressure (-3.2 mmHg (-4.2%)), and low frequency/high frequency (LF/HF) (Ln ratio) (p < 0.05). Post-study, the HEX group had higher HF (Ln ms2) than the CON, adjusted for pre-study value and age (p < 0.05). Post-study, the supine-standing ratio (SSR) of LFn (normalized unit) in the HEX group was greater than that in the LEX and CON groups, while the SSR of LF/HF in the HEX group was greater than the CON (p < 0.05). In conclusion, high-intensity RT can improve resting heart rate and HRV by enhancing cardiac vagal control. High-intensity RT might also improve the orthostatic response in terms of HRV. High intensity RT might assist ANS modification and could perhaps decrease the risks of cardiovascular disease and orthostatic intolerance.

Interactive Effect of Corticosterone and Lactate on Regulation of Testosterone Production in Rat Leydig Cells.

The increasing intensity of exercise enhanced corticosterone and lactate production in both humans and rodents. Our previous studies also demonstrated that lactate could stimulate testosterone production in vivo and in vitro. However, the production of testosterone in response to combined corticosterone and lactate on Leydig cells, and underlying molecular mechanisms are remained unclear. This study investigated the changes in testosterone levels of Leydig cells upon exposure to lactate, corticosterone or combination of both, and revealed the detailed mechanisms. Leydig cells were isolated from rat testes, and treated with different concentrations of lactate (2.5-20 mM), cortiosterone (10-9 -10-4 M) and lactate plus corticosterone. The production of testosterone were assayed by radioimmunoassay, and the key molecular proteins, including luteinizing hormone receptor (LHR), protein kinase A (PKA), steroidogenic acute regulatory protein (StAR), and cholesterol P450 side-chain cleavage enzyme (P450scc) involved in testosterone production were performed by Western blot. Results showed that testosterone levels were significantly increased with lactate, while decresed with corticosterone and lactate plus corticosterone treatment. Protein expressions of LHR and P450scc were upregulated with lactate treatment. However, PKA and P450scc were downregulated by lactate plus corticosterone treatment. This downregulation was followed by decreased testoterone levels in Leydig cells. Furthermore, acetylated cAMP, which activates testosterone production was increased with lactate, but not altered by conrtiosterone. Our findings conclude that corticosterone may interfere with lactate, and restrict lactate-stimulated testosterone production in Leydig cells. J. Cell. Physiol. 232: 2135-2144, 2017. © 2016 Wiley Periodicals, Inc.

Effects of acrolein on the production of corticosterone in male rats.

Acrolein, an α, ß-unsaturated aldehyde, exists in a wide range of sources. Acrolein can be not only generated from all types of smoke but also produced endogenously from the metabolism by lipid peroxidation. The cellular influence of acrolein is due to its electrophilic character via binding to and depleting cellular nucleophiles. Although the toxicity of acrolein has been extensively studied, there is relatively little information about its impact on hormone release. This study aimed at the effect of acrolein on hypothalamic-pituitary-adrenal (H-P-A) axis. In an in vivo study, male rats were administrated with acrolein for 1 or 3days. The plasma corticosterone in response to a single injection of adrenocorticotropic hormone (ACTH) increased slowly in acrolein-pretreated rats than in control rats. Further investigating the steroidogenic pathway, the protein expressions of steroidogenic acute regulatory protein (StAR) and the upper receptor-melanocortin 2 receptor (MC2R) were attenuated in acrolein-treated groups. Another experiment using trilostane showed less activity of P450scc in zona fasciculata-reticularis (ZFR) cells in acrolein-treated groups. In addition to the suppressed ability of corticosterone production in ZFR cells, acrolein even had extended influence at higher concentrations. The lower ACTH was observed in the plasma from acrolein-pretreated rats. In an in vitro study, ZFR cells were incubated with acrolein and the results showed that corticosterone concentrations in media were decreased in a dose-dependent manner. Acrolein also desensitized the response of the ZFR cells to ACTH. These results suggested that acrolein decreased the releasing ability of corticosterone via an inhibition on the response of ZFR cells to ACTH and the reduction of protein expressions of StAR and MC2R as well as the activity of P450scc in rat ZFR cells. The present evidences showed that the H-P-A axis was affected by the administration of acrolein.

Effects of acrolein on aldosterone release from zona glomerulosa cells in male rats.

A positive correlation between smoking and hypertension has been well established. Acrolein is a major toxic volatile compound found in cigarette smoke. Human exposure to low levels of acrolein is unavoidable due to its production in daily activities, such as smoke from industrial, hot oil cooking vapors, and exhaust fumes from vehicles. The toxicity and the action mechanism of acrolein to induce apoptosis have been extensively studied, but the effects of acrolein on hypertension are still unknown. The present study aimed to examine the effects of acrolein on aldosterone release both in vivo and in vitro. Male rats were divided into three groups, and intraperitoneally injected with normal saline, or acrolein (2mg/kg) for 1 (group A-1) or 3 (group A-3) days, respectively. After sacrificing, rat blood samples were obtained to measure plasma aldosterone and angiotensin II (Ang II) levels. Zona glomerulosa (ZG) cells were prepared from rat adrenal cortex, and were incubated with or without stimulants. We found that the serum aldosterone was increased by 1.2-fold (p<0.05) in A-3 group as compared to control group. Basal aldosterone release from ZG cells in A-3 group was also increased significantly. Moreover, acrolein enhanced the stimulatory effects of Ang II and 8-bromo-cyclic AMP on aldosterone secretion from ZG cells prepared in both A-1 and A-3 groups. Furthermore, the enzyme activity of P450scc, the rate-limiting step of aldosterone synthesis, was elevated after acrolein injection. Plasma level of Ang II was increased in both A-1 and A-3 groups. These results suggested that acrolein exposure increased aldosterone production, at least in part, through elevating the level of plasma Ang II and stimulating steroidogenesis pathways.

Effects of armepavine against hepatic fibrosis induced by thioacetamide in rats.

The aim of this study was to investigate if armepavine (Arm, C19H23O3N) could exert inhibitory effects against hepatic fibrosis in rats. A cell line of rat hepatic stellate cells (HSC-T6) was stimulated with tumour necrosis factor-α (TNF-α) to evaluate the inhibitory effects of Arm. Rats were injected with thioacetamide (TAA; 300 mg/kg, intraperitoneally) thrice a week for 4 weeks to induce hepatic fibrosis, with Arm (3 or 10 mg/kg) given by gavage twice a day. Liver sections were taken for western blotting, fibrosis scoring and immunofluorescence staining. Arm (1-10 µm) concentration-dependently attenuated TNF-α-stimulated: (i) protein expressions of α-smooth muscle actin (α-SMA), collagen type I and angiopoietin-1; (ii) H2O2 production; and (iii) NF-κB, JunD and C/EBPß (cytidine-cytidine-adenosine-adenosine-thymidine (CCAAT)/enhancer binding protein-ß (EBPß)) nuclear translocations in HSC-T6 cells. In vivo Arm treatment significantly reduced plasma aspartate transaminase and alanine transaminase levels, hepatic α-SMA expression and collagen contents, and fibrosis scores of TAA-injected rats. Moreover, Arm treatment decreased α-SMA- and NF-κB-positive cells in immunohistochemical staining, and mRNA expression levels of IL-6, TGF-ß1, TIMP-1, col1α2, iNOS and ICAM-1 genes, but up-regulated the metallothionein gene in the livers of TAA-injected rats. Our results indicated that Arm exerted both in vitro and in vivo antifibrotic effects in rats, with inhibition of NF-κB, JunD and C/EBPß pathways.

Inhibitory effects of armepavine against hepatic fibrosis in rats.

Activation of hepatic stellate cells (HSCs) plays a crucial role in liver fibrogenesis. armepavine (Arm, C19H23O3N), an active compound from Nelumbo nucifera, has been shown to exert immunosuppressive effects on T lymphocytes and on lupus nephritic mice. The aim of this study was to investigate whether Arm could exert anti-hepatic fibrogenic effects in vitro and in vivo. A cell line of rat HSCs (HSC-T6) was stimulated with tumor necrosis factor-alpha (TNF-alpha) or lipopolysaccharide (LPS) to evaluate the inhibitory effects of Arm. An in vivo therapeutic study was conducted in bile duct-ligated (BDL) rats. BDL rats were given Arm (3 or 10 mg/kg) by gavage twice daily for 3 weeks starting from the onset of BDL. Liver sections were taken for fibrosis scoring, immuno-fluorescence staining and quantitative real-time mRNA measurements. In vitro, Arm (1-10 microM) concentration-dependently attenuated TNF-alpha- and LPS-stimulated alpha-SMA protein expression and AP-1 activation by HSC-T6 cells without adverse cytotoxicity. Arm also suppressed TNF-alpha-induced collagen collagen deposition, NFkappaB activation and MAPK (p38, ERK1/2, and JNK) phosphorylations. In vivo, Arm treatment significantly reduced plasma AST and ALT levels, hepatic alpha-SMA expression and collagen contents, and fibrosis scores of BDL rats as compared with vehicle treatment. Moreover, Arm attenuated the mRNA expression levels of col 1alpha2, TGF-beta1, TIMP-1, ICAM-1, iNOS, and IL-6 genes, but up-regulated metallothionein genes. Our study results showed that Arm exerted both in vitro and in vivo antifibrotic effects in rats, possibly through anti-NF-kappaB activation pathways.

The hepatoprotective effect of Bupleurum kaoi, an endemic plant to Taiwan, against dimethylnitrosamine-induced hepatic fibrosis in rats.

In the present study, three materials extracted or isolated from the roots of B. kaoi, an endemic plant to Taiwan, were used to be examined the hepatoprotective effect against dimethylnitrosamine (DMN)-induced hepatic fibrosis in rats, they were water extract (BKW), polysaccharide-enriched fractions (BKP) and saponin-enriched fractions (BKS). After treated with DMN for 4 weeks, the levels of aminotrasferases (GOT, GPT) were significantly elevated in serum, and the levels of total protein (TP) and albumin were significantly decreased in serum and liver homogenates. Furthermore, the collagen contents were significantly elevated in liver homogenates and corresponded to the hepatofibrotic pathological examination. As the results showed, treated with groups of BKW, BKP, BKS markedly reduced GOT, GPT levels in rats serum. In addition, treated with groups of BKW, BKP, BKS markedly raised TP levels in rats serum and liver homogenates. Furthermore, treated with groups of BKW, BKP markedly raised albumin levels in rats serum and liver homogenates. Treated with groups of BKW, BKP, BKS markedly raised interferon-gamma (IFN-gamma) levels in rats serum, where only BKS and silymarin markedly raised interkeukin-10 (IL-10) levels in rats serum compared to that of DMN treated rats. None of test materials of B. kaoi except silymarin reduced the malondialdehyde (MDA) levels, but BKW, BKP markedly raised hepatic glutathione (GSH) levels to reveal the activity of anti-lipid peroxidation. Otherwise, treated with groups of BKW, BKP, BKS significantly reduced collagen contents in rats liver homogenates. In conclusion, B. kaoi demonstrated the anti-inflammatory and anti-fibrotic activities followed by anti-oxidant activity of enhanced GSH production, enhanced the liver cell regeneration and concerned with regulations of INF-gamma and IL-10. The ability of hepatoprotective and anti-fibrotic activities of B. kaoi are higher than B. chinense, a Bupleuri Radix imported from China to Taiwan.

The antiproliferative activity of saponin-enriched fraction from Bupleurum Kaoi is through Fas-dependent apoptotic pathway in human non-small cell lung cancer A549 cells.

Bupleuri Radix (Chai-hu in Chinese and Saiko in Japanese) is one of the most important traditional Chinese crude drugs for treating hepatitis malaria and intermittent fever. B. kaoi is one of the Bupleurum spp. families locally found in Taiwan. The effects of saponin-enriched fraction (SEF) from Bupleurum Kaoi in human non-small cell lung cancer A549 cells were investigated in this study. An enhancement in Fas and its two forms of ligands, membrane-bound Fas ligand (mFasL) and soluble Fas ligand (sFasL), was responsible for the apoptotic effect induced by SEF. Taken together, our study suggests that the activity of the Fas/Fas ligand apoptotic system may participate in the antiproliferative activity of SEF in A549 cells.