Chemosensory control by commissural nucleus of the solitary tract in rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Commissural NTS lesions enhance the pressor response to central cholinergic and adrenergic activation

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Influence of arginine vasopressin receptors and angiotensin receptor subtypes on the water intake and arterial blood pressure induced by vasopressin injected into the lateral septal area of the rat

In this study we investigated the influence of d(CH2)(5)-Tyr(Me)-[Arg(8)]vasopressin (AAVP) and [adamanteanacetyl(1),0-ET-DTyr(2), Val(4), aminobutyryl(6), Arg(8,9)]-[Arg(8)]vasopressin (ATAVP), which are antagonists of vasopressin V-1 and V-2 receptors, and the effects of losartan, a selective angiotensin AT(1) receptor antagonist, and CGP42112A, a selective AT(2) receptor antagonist, injected into the lateral septal area (LSA) on thirst and hypertension induced by [Arg(8)]vasopressin (AVP). AAVP and ATAVP injected into the LSA reduced the drinking responses elicited by injecting AVP into the LSA. Both the AT(1) and AT(2) ligands administered into the LSA elicited a concentration-dependent decrease in the water intake induced by AVP injected into the LSA, but losartan was more effective than CGP42112A. The increase in MAP, due to injection of AVP into the LSA, was reduced by prior injection of AAVP from 18 +/- 1 to 6 +/- 1 mm Hg. Losartan injected into the LSA prior to AVP reduced the increase in MAP to 7 +/- 0.8 mm Hg. ATAVP and CGP42112A produced no changes in the pressor effect of AVP. These results suggest that the dipsogenic effects induced by injecting AVP into the LSA were mediated primarily by AT(1) receptors. However, doses of losartan were more effective when combined with CGP42112A than when given alone, suggesting that the thirst induced by AVP injections into LSA may involve activation of multiple AVP and angiotensin II receptor subtypes. The pressor response of AVP was reduced by losartan and by AAVP. CGP42112A and ATAVP did not change the AVP pressor response. These results suggest that facilitator effects of AVP on water intake are mediated through the activation of V-1 receptors and that the inhibitory effect requires V-2 receptors. The involvement of AT(1) and AT(2) receptors can be postulated. Based on the present findings, we suggest that the AVP in the LSA may play a role in the control of water and arterial blood pressure balance. (C) 2004 Elsevier B.V. All rights reserved.

Estrous behavior and the estrus-to-ovulation interval in Nelore cattle (Bos indicus) with natural estrus or estrus induced with prostaglandin F2 alpha or norgestomet and estradiol valerate

Estrous behavior and the estrus-to-ovulation interval are essential for estimating the best time to artificially inseminate cattle. Because these parameters are not well characterized in the Nelore breed (Bos indicus), the main purpose of the this study was to determine the estrus-to-ovulation interval in Nelore heifers and cows with natural estrus or with estrus induced by treatments with PGF2 alpha or norgestomet and estradiol valerate (NEV). The cows and heifers were observed continuously (24 h a day) to determine the onset of estrus and to study estrous behavior in the cows. Ten hours after the start of estrus the ovaries were scanned every 2 h by ultrasonography to monitor the dominant follicle until ovulation. Blood samples were collected periodically to determine progesterone levels by RIA. Administration of PGF2 alpha (2 injections, 11 days apart) did not induce estrus in most Nelore females in spite of the presence of functional CL, indicated by progesterone concentrations above 6.0 ng/ml in 25 of 28 animals. Treatment with NEV induced high sexual receptivity in cows (10/11), but only 66% ovulated. Cows with natural or induced estrus exhibited behavioral estrus of 10.9 +/- 1.4 h, and ovulation occurred 26.6 +/- 0.44 h (n = 26) after the onset of estrus. In most of the cows (53.8%) estrus began at night (between 1801 and 600 h), and 34.6% it started and finished during the night. It is concluded that in Nelore females ovulation occurs approximately 26 h after the onset of estrus. Additionally, estrous behavior is shorter than in European breeds, and there is a high incidence of estrus at night, which makes it difficult to detect and, consequently, impairs Al in Nelore cattle. The observation that a high percentage of Nelore females with an active CL did not respond to usual dosages of PGF2 alpha warrants further investigation. (C) 1998 by Elsevier B.V.

GROWTH HORMONE ATTENUATES MYOCARDIAL FIBROSIS IN RATS WITH CHRONIC PRESSURE OVERLOAD-INDUCED LEFT VENTRICULAR HYPERTROPHY

1. The role of growth hormone (GH) in cardiac remodelling and function in chronic and persistent pressure overload-induced left ventricular hypertrophy has not been defined. The aim of the present study was to assess short-term GH treatment on left ventricular function and remodelling in rats with chronic pressure overload-induced hypertrophy.2. Twenty-six weeks after induction of ascending aortic stenosis (AAS), rats were treated with daily subcutaneous injections of recombinant human GH (1 mg/kg per day; AAS-GH group) or saline (AAS-P group) for 14 days. Sham-operated animals served as controls. Left ventricular function was assessed by echocardiography before and after GH treatment. Myocardial fibrosis was evaluated by histological analysis.3. Before GH treatment, AAS rats presented similar left ventricular function and structure. Treatment of rats with GH after the AAS procedure did not change bodyweight or heart weight, both of which were higher in the AAS groups than in the controls. After GH treatment, posterior wall shortening velocity (PWSV) was lower in the AAS-P group than in the control group. However, in the AAS-GH group, PWSV was between that in the control and AAS-P groups and did not differ significantly from either group. Fractional collagen (% of total area) was significantly higher in the AAS-P and AAS-GH groups compared with control (10.34 +/- 1.29, 4.44 +/- 1.37 and 1.88 +/- 0.88%, respectively; P < 0.05) and was higher still in the AAS-P group compared with the AAS-GH group.4. The present study has shown that short-term administration of GH to rats with chronic pressure overload-induced left ventricular hypertrophy induces cardioprotection by attenuating myocardial fibrosis.

Growth hormone attenuates skeletal muscle changes in experimental chronic heart failure

Objective: This study evaluated the effects of growth hormone (GH) on morphology and myogenic regulatory factors (MRF) gene expression in skeletal muscle of rats with ascending aortic stenosis (AAS) induced chronic heart failure.Design: Male 90-100 g Wistar rats were subjected to thoracotomy. AAS was created by placing a stainless-steel clip on the ascending aorta. Twenty five weeks after surgery, rats were treated with daily subcutaneous injections of recombinant human GH (2 mg/kg/day; AAS-GH group) or saline (AAS group) for 14 days. Sham-operated animals served as controls. Left ventricular (LV) function was assessed before and after treatment. IGF-1 serum levels were measured by ELISA. After anesthesia, soleus muscle was frozen in liquid nitrogen. Histological sections were stained with HE and picrosirius red to calculate muscle fiber cross-sectional area and collagen fractional area, respectively. MRF myogenin and MyoD expression was analyzed by reverse transcription PCR.Results: Body weight was similar between groups. AAS and AAS-GH groups presented dilated left atrium, left ventricular (LV) hypertrophy (LV mass index: Control 1.90 +/- 0.15; AAS 3.11 +/- 0.44; AAS-GH 2.94 +/- 0.47 g/kg; p < 0.05 AAS and AAS-GH vs. Control), and reduced LV posterior wall shortening velocity. Soleus muscle fiber area was significantly lower in AAS than in Control and AAS-GH groups; there was no difference between AAS-GH and Control groups. Collagen fractional area was significantly higher in MS than Control; AAS-GH did not differ from both Control and AAS groups. Serum IGF-1 levels decreased in AAS compared to Control. MyoD mRNA was significantly higher in AAS-GH than AAS; there was no difference between AAS-GH and Control groups. Myogenin mRNA levels were similar between groups.Conclusion: In rats with aortic stenosis-induced heart failure, growth hormone administration increases MyoD gene expression above non-treated animal levels, preserves muscular trophism and attenuates interstitial fibrosis. These results suggest that growth hormone may have a potential role as an adjuvant therapy for chronic heart failure. (C) 2009 Elsevier Ltd. All rights reserved.

Increased glucose synthesis in renal tubule fragments from hyperthyroid rats

Rates of glucose synthesis from several substrates were examined in renal tubule fragments from hyperthyroid rats. A hyperthyroid state was induced by daily intraperitoneal injections of thyroxine (T-4) (100 mu g/100 g body weight) for 14 days. At the end of the experimental period, plasma triiodothyronine and T-4 levels were six and eight times higher, respectively, than initial values. Hyperthyroid rats gained less weight and had lower blood glucose despite an increased food intake. In both control and hyperthyroid rats, rates of glucose production by renal tubule fragments were higher with glutamine and glycerol than with lactate, alanine, or glutamate. T-4 treatment induced a significant increase in the de novo glucose synthesis from all substrates, except glutamine. The highest percent increase was obtained with alanine (64%), compared with 31-40% for glutamate, lactate, and glycerol. The T-4 treatment induced increase in glucose synthesis by renal tubule fragments suggests that renal gluconeogenesis contributes to enhance glucose production in hyperthyroidism.

Polysaccharide-rich fraction of Agaricus brasiliensis enhances the candidacidal activity of murine macrophages

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Effects of ginger (Zingiber officinale Roscoe) on DNA damage and development of urothelial tumors in a mouse bladder carcinogenesis model

Extracts of the spice ginger (Zingiber officinale Roscoe) are rich in gingerols and shogaols, which exhibit antioxidant, anti-inflammatory, antifungal, anti mycobacterial, and anticarcinogenic proprieties. The present study evaluated the chemoprotective effects of a ginger extract on the DNA damage and the development of bladder cancer induced by N-butyl-N-(4-hydroxibutyl) nitrosamine (BBN)/N-methyl-N-nitrosourea (MNU) in male Swiss mice. Groups G1-G3 were given 0.05% BBN in drinking water for 18 weeks and four i.p. injections of 30 mg/kg body weight MNU at 1, 3, 10, and 18 weeks. Group G4 and G5 received only the BBN or MNU treatments, respectively, and groups G6 and G7 were not treated with BBN or MNU. Additionally, Groups G2, G3, and G6 were fed diets containing 1, 2, and 2% ginger extract, respectively, while Groups G1, G4, G5, and G7 were fed basal diet. Samples of peripheral blood were collected during the experiment for genotoxicity analysis; blood collected 4 hr after each MNU dose was used for the analysis of DNA damage with the Comet assay (assay performed on leukocytes from all groups), while reficulocytes collected 24 hr after the last MNU treatment of Groups G5-G7 were used for the micronucleus assay. At the end of the experiment, the urinary bladder was removed, fixed, and prepared for histopathological, cell proliferation, and apoptosis evaluations. Ginger by itself was not genotoxic, and it did not alter the DNA damage levels induced by the BBN/MNU treatment during the course of the exposure. The incidence and multiplicity of simple and nodular hyperplasia and transitional cell carcinoma (TCC) were increased by the BBN/MNU treatment, but dietary ginger had no significant effect on these responses. However, in Group G2 (BBN/MNU/2% ginger-treated group), there was an increased incidence of Grade 2 TCC. The results suggest that ginger extract does not inhibit the development of BBN-induced mouse bladder tumors.

Fertility of rat epididymal sperm after chemically and surgically induced sympathectomy

Guanethidine, a chemical that selectively blocks sympathetic noradrenergic neurons, was used to investigate the role of sympathetic innervation in the fertility of rat epididymal sperm, using both natural mating and in utero insemination protocols. This animal model correlates, at least in part, with spinal cord injury (SCI) in men. Adult male rats were treated daily by i.p. injections, for 21 or 42 days, with 0 or 6.25 mg/kg guanethidine. To compare the effects of guanethidine-induced sympathectomy with those following surgically induced sympathectomy, the inferior mesenteric ganglion and the proximal hypogastric nerves were removed in another group of rats. Both chemically and surgically induced sympathectomy increased the weight of the epididymis and seminal vesicles/coagulating glands as well as the number and the transit time of cauda epididymal sperm. Neither serum testosterone levels nor LH was affected by treatment with guanethidine. Using natural mating, no litters were produced by guanethidine-treated rats. Chemically denervated rats failed to produce copulatory plugs or ejaculate into the uterus. However, distal cauda epididymal sperm from chemically or surgically denervated rats displayed normal fertilization ability (80%) using in utero inseminations. In addition, the sperm of denervated rats did not show abnormal sperm chromatin structure using an assay that detects DNA damage. We conclude that sympathectomy delays the transit of sperm through the cauda epididymidis and produces ejaculatory dysfunction but does not compromise sperm quality in the distal cauda epididymidis. Moreover, these data provide compelling evidence that there is no association between the prolonged transit time of sperm within the epididymis, i.e., pre-ejaculatory sperm aging, and the fertility of those sperm, which has important implications for artificial insemination using sperm from men with SCI.

Rat epididymal sperm quantity, quality, and transit time after guanethidine-induced sympathectomy

Guanethidine, a chemical that selectively abolishes peripheral noradrenergic nerves, was used to investigate the role of sympathetic innervation in the maintenance of epididymal sperm quantity and quality. Four groups of 10 adult male rats each were treated daily for 21 days, by i.p. injections, with either 0 (saline vehicle), 6.25, 12.5, or 25 mg/kg guanethidine. Norepinephrine content was reduced to undetectable levels in the cauda epididymidis in all guanethidine groups after 3 wk of treatment and was reduced to 7.4% of the control values after 1 wk of 6.25 mg/kg treatment. While body weight gain was significantly decreased at 12.5 and 25 mg/kg compared to that in controls, there was a significant increase in the weights of the seminal vesicles/coagulating glands in all treated groups. The number of homogenization-resistant spermatids per testis and the daily sperm production per testis remained unchanged. The weight of the epididymis was significantly increased at 6.25 and 12.5 mg/kg. Moreover, the number of cauda epididymal sperm and the transit time were increased significantly at 6.25 mg/kg (10.2 days) compared to values in the control cauda (6.3 days). Neither serum testosterone levels nor LH was affected in a dosage-related manner. There were no effects of guanethidine treatment on cauda epididymal sperm motility or morphology. A quantitative analysis of detergent-extracted cauda epididymal sperm proteins by SDS-PAGE revealed no differences, but there were diminutions in seven proteins in homogenates of caput/ corpus tissue. Histologic analysis of testis and epididymis sections revealed no differences between control and denervated animals. In a subsequent experiment the lowest effective dosage (6.25 mg/kg) was given to rats for 1 wk, and an increased number of cauda epididymal sperm and a delay in sperm transit were observed. Our results indicate that low-dosage guanethidine exposure denervates the epididymis within 1 wk, thereby delaying epididymal transit; however, neither 1- nor 3-wk exposure produces qualitative changes in the sperm.

Exercise preconditioning modulates genotoxicity induced by doxorubicin in multiple organs of rats

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Highly Sensitive Neurotransmitters Analysis at Platinum-Ultramicroelectrodes Arrays

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Baroreflex control of heart rate in the broad-nosed caiman Caiman latirostris is temperature dependent

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Role of central nitric oxide in behavioral thermoregulation of toads during hypoxia

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)