The superior beneficial effects of exercise training versus hormone replacement therapy on skeletal muscle of ovariectomized rats.

Previous studies have highlighted the positive effects of Estradiol (E2) replacement therapy and physical exercise on skeletal muscle during menopause. However, the comparison effects of exercise training (ET) and estradiol replacement therapy during menopause on skeletal muscle have not been investigated to date. This study aimed to compare the effects of endurance exercise training versus E2 replacement therapy on mitochondrial density, redox status, and inflammatory biomarkers in the skeletal muscle of ovariectomized rats. Thirty female Wistar rats (12-week-old) were randomly assigned into three groups: Untrained ovariectomized rats (UN-OVX, n = 10); untrained ovariectomized rats treated with estradiol replacement therapy (E2-OVX); and, trained ovariectomized rats (TR-OVX). After ovariectomy, the E2-OVX rats were treated subcutaneously with E2 (implanted Silastic® capsule containing 360 µg of 17ß-estradiol/mL) while the TR-OVX group performed an exercise training protocol (50-70% of maximal running speed on a treadmill, 60 min/day, 5 days/week for 8 weeks). After euthanasia, the soleus muscle was processed for histological and biochemical evaluations. Only exercise prevented the reduction of maximal oxygen consumption and increased mechanical efficiency (ME). While mitochondrial muscle density, total antioxidant capacity (FRAP), catalase (CAT) activity, and interleukin 10 levels were higher in TR-OVX, only OVX-E2 presented higher CAT activity and lower interleukin 6 levels. Endurance exercise training compared with E2 replacement therapy maintains the aerobic capacity improving the ME of OVX rats. In addition, only endurance exercise training raises the skeletal muscle mitochondrial content and tends to balance the redox and inflammatory status in the skeletal muscle of OVX rats.

Tibolone has anti-inflammatory effects in estrogen-deficient female rats on the natriuretic peptide system and TNF-alpha.

Cardiovascular and immune system abnormalities have been reported in females with estrogen deficiency. To control these disorders in post-menopausal women, hormone replacement therapy (HRT) has been used. Tibolone has been used as a HRT, but the effects of tibolone on the natriuretic peptide system have not been determined. We investigated the effects of tibolone on the natriuretic peptide system and pro-inflammatory cytokines in ovariectomized (OVX) rats. Female rats were divided into four groups: SHAM, OVX, OVX treated with 17ß-estradiol (OVX+E: 14 days) and OVX treated with tibolone (OVX+T: 14 days) beginning 21 days after ovariectomy. On day 35, blood was collected to determine atrial natriuretic peptide (ANP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) levels. In addition, tissues were collected for determining ANP, natriuretic peptide receptor type-A (NPR-A), and NPR type-C (NPR-C) gene expression levels by RT-PCR. The cytokine levels of both IL-6 and TNF-α were increased in OVX animals. In comparison, IL-6 and TNF-α levels were reduced in OVX+E animals. TNF-α levels were reduced similarly in OVX+T animals, but IL-6 levels remained elevated in this group. The concentrations of ANP in the left atrium tissue and plasma were decreased after ovariectomy, as were ANP mRNA levels in the left atrium and NPR-A mRNA levels in kidney. No variation in NPR-C gene expression in the kidney tissue was observed among the groups. Tibolone and 17ß-estradiol effectively increased plasma ANP and ANP mRNA levels in the left atrium, but did not normalize renal NPR-A levels. Since HRT with tibolone normalizes plasma ANP and serum TNF-alpha levels our results suggest that treatment with tibolone has anti-inflammatory effects and could prevent cardiovascular disease in the long-term.

The effect of saponins from Ampelozizyphus amazonicus Ducke on the renal Na+ pumps' activities and urinary excretion of natriuretic peptides.

BACKGROUND: In a previous study, we showed that a saponin mixture isolated from the roots of Ampelozizyphus amazonicus Ducke (SAPAaD) reduces urine excretion in rats that were given an oral loading of 0.9 % NaCl (4 ml/100 g body weight). In the present study, we investigated whether atrial natriuretic peptides (ANP) and renal ATPases play a role in the SAPAaD- induced antidiuresis in rats. METHODS: To evaluate the effect of SAPAaD on furosemide-induced diuresis, Wistar rats (250-300 g) were given an oral loading of physiological solution (0.9 % NaCl, 4 ml/100 g body weight) to impose a uniform water and salt state. The solution containing furosemide (Furo, 13 mg/kg) was given 30 min after rats were orally treated with 50 mg/kg SAPAaD (SAPAaD + Furo) or 0.5 ml of 0.9 % NaCl (NaCl + Furo). In the SAPAaD + NaCl group, rats were pretreated with SAPAaD and 30 min later they received the oral loading of physiological solution. Animals were individually housed in metabolic cages, and urine volume was measured every 30 min throughout the experiment (3 h). To investigate the role of ANP and renal Na(+) pumps on antidiuretic effects promoted by SAPAaD, rats were given the physiological solution (as above) containing SAPAaD (50 mg/kg). After 90 min, samples of urine and blood from the last 30 min were collected. Kidneys and atria were also removed after previous anesthesia. ANP was measured by radioimmunoassay (RIA) and renal cortical activities of Na(+)- and (Na(+),K(+))-ATPases were calculated from the difference between the [32P] Pi released in the absence and presence of 1 mM furosemide/2 mM ouabain and in the absence and presence of 1 mM ouabain, respectively. RESULTS: It was observed that SAPAaD inhibited furosemide-induced diuresis (at 90 min: from 10.0 ± 1.0 mL, NaCl + Furo group, n = 5, to 5.9 ± 1.0 mL, SAPAaD + Furo group n = 5, p < 0.05), increased both Na(+)-ATPase (from 25.0 ± 5.9 nmol Pi.mg(-1).min(-1), control, to 52.7 ± 8.9 nmol Pi.mg(-1).min(-1), p < 0.05) and (Na(+),K(+))-ATPase (from 47.8 ± 13.3 nmol Pi.mg(-1).min(-1), control, to 79.8 ± 6.9 nmol Pi .mg(-1).min(-1), p < 0.05) activities in the renal cortex. SAPAaD also lowered urine ANP (from 792 ± 132 pg/mL, control, to 299 ± 88 pg/mL, p < 0.01) and had no effect on plasma or atrial ANP. CONCLUSION: We concluded that the SAPAaD antidiuretic effect may be due to an increase in the renal activities of Na(+)- and (Na(+),K(+))-ATPases and/or a decrease in the renal ANP.

A panic attack-like unusual stress reaction.

Ever since the seminal studies of Hans Selye, activation of hypothalamus-pituitary-adrenal (HPA) axis is emblematic of stress. Consequently, the lack of HPA axis responses following the undisputable psychological stress of a panic attack stands out as one of the most intriguing findings of contemporary psychiatry. On the other hand, the defensive behaviors and aversive emotions produced by stimulation of the dorsal periaqueductal gray matter (DPAG) have been proposed as a model of panic attacks. Therefore, we examined whether the plasma levels of 'stress hormones' corticotropin and prolactin show any change following the DPAG-evoked freezing and flight behaviors of the rat. Rats bearing an electrode into the DPAG and an intra-atrial catheter were stimulated at 9:00 a.m., 18-24 h after the catheter implantation. Blood samples were withdrawn just before 1-min stimulation of DPAG, immediately after (5 or 15 min) and throughout 3 to 27 h following stimulation. In another experiment, samples were withdrawn either before or following a prolonged stimulation (5 min) of the DPAG with flight threshold intensity. Hormones were measured by either chemiluminescent or double-antibody immunoassays. Hormone plasma levels following freezing and flight behaviors were compared to those of resting or restraint-stressed rats. Data show that stress hormones remain unaltered following the DPAG-evoked defensive behaviors. Not even the 5-min stimulation of DPAG with the flight threshold intensity changed corticotropin plasma levels significantly. As far as we known, this is the first demonstration of the lack of stress hormone responses following the intense emotional arousal and physical exertion of a fear-like behavior in rats. Data add new evidence of DPAG involvement in spontaneous panic attacks.

Medial preoptic area adrenergic receptors modulate glycemia and insulinemia in freely moving rats.

In order to investigate the role of medial preoptic area (MPOA) adrenoceptors in regulation of plasma glucose and insulin secretion, we injected 40 nmol of noradrenaline, clonidine or isoproterenol into the MPOA of freely moving Wistar rats. The animals were fitted with chronic jugular catheters for blood sampling and unilateral intracerebral cannulae placed into MPOA. The results showed that noradrenaline injection into MPOA produced a rapid increase in plasma glucose levels and insulin secretion, reaching a peak at 15 min post stimulus (25% over basal, P<0.01) for plasma glucose and at 30 min for insulin secretion (94% over basal, P<0.05). Injection of the alpha2-adrenergic agonist clonidine into MPOA produced a faster, more intense and longer-lasting hyperglycemic response (69% over basal, P<0.01). In contrast to the noradrenaline effect on insulin secretion, clonidine markedly decreased plasma insulin levels, reaching a maximal suppression at 10 min (72% below basal, P<0.01). On the other hand, the beta-adrenergic agonist isoproterenol only produced a small, transient increase in plasma glucose levels. When rats were pre-treated with guanethidine (10 mg/100 g, i.p.), despite reduced baseline of plasma glucose (35% smaller then control group, P<0.01) and increased plasma insulin baseline (300% higher then control group, P<0.01), they still showed a hyperglycemic response to noradrenaline injection into MPOA. We conclude that the activation of preoptic alpha2-adrenoceptors induced hyperglycemia and inhibit insulin secretion, probably by activation of the sympathoadrenal system that cannot be blocked by prior administration of guanethidine.

Acute metabolic effects of thiopental anesthesia on fed and fasted rats chronically treated with bromocriptine.

We investigated the acute effects of thiopental anesthesia (4 mg/100 g, i.v.) on plasma glucose, insulin, triacylglycerol, and prolactin levels in rats treated with bromocriptine (BR) (0.4 mg/100 g body wt, i.p., for two weeks). Thiopental anesthesia induced a rapid increase in plasma insulin that was more pronounced in the animals treated with BR (116%, P <0.05). Thiopental anesthesia also produced a 55% decreased in plasma prolactin levels (P <0.01) in control fed rats, and a 22% reduction in plasma triacylglycerol (P <0.05) in both controls and BR-treated rats. We conclude that BR may constitute and additional sympatholytic factor in animals submitted to thiopental anesthesia.

Brain natriuretic peptide and left ventricular dysfunction in Chagas' disease.

Left ventricular dysfunction in Chagas' disease is common but can be difficult to detect. We investigated whether measurement of plasma brain natriuretic peptide (BNP) could identify patients with left ventricular dysfunction who need further investigation or treatment. Among patients with an abnormal electrocardiogram or chest radiograph, a BNP concentration of 60.7 pmol/L or higher has a sensitivity and positive predictive value of 80%, and specificity and negative predictive value of 97%. Measurement of plasma BNP concentration could be a useful method to screen patients with Chagas' disease.