Effects of One Resistance Exercise Session on Vascular Smooth Muscle of Hypertensive Rats

AbstractBackground:Hypertension is a public health problem and increases the incidence of cardiovascular diseases.Objective:To evaluate the effects of a resistance exercise session on the contractile and relaxing mechanisms of vascular smooth muscle in mesenteric arteries of NG-nitro L-arginine methyl ester (L-NAME)-induced hypertensive rats.Methods:Wistar rats were divided into three groups: control (C), hypertensive (H), and exercised hypertensive (EH). Hypertension was induced by administration of 20 mg/kg of L-NAME for 7 days prior to experimental protocols. The resistance exercise protocol consisted of 10 sets of 10 repetitions and intensity of 40% of one repetition maximum. The reactivity of vascular smooth muscle was evaluated by concentration‑response curves to phenylephrine (PHEN), potassium chloride (KCl) and sodium nitroprusside (SNP).Results:Rats treated with L-NAME showed an increase (p < 0.001) in systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial pressure (MAP) compared to the initial period of induction. No difference in PHEN sensitivity was observed between groups H and EH. Acute resistance exercise reduced (p < 0.001) the contractile response induced by KCl at concentrations of 40 and 60 mM in group EH. Greater (p < 0.01) smooth muscle sensitivity to NPS was observed in group EH as compared to group H.Conclusion:One resistance exercise session reduces the contractile response induced by KCl in addition to increasing the sensitivity of smooth muscle to NO in mesenteric arteries of hypertensive rats.

The Labdane Ent-3-Acetoxy-Labda-8(17), 13-Dien-15-Oic Decreases Blood Pressure In Hypertensive Rats

Abstract Background: Labdane-type diterpenes induce lower blood pressure via relaxation of vascular smooth muscle; however, there are no studies describing the effects of labdanes in hypertensive rats. Objective: The present study was designed to investigate the cardiovascular actions of the labdane-type diterpene ent-3-acetoxy-labda-8(17), 13-dien-15-oic acid (labda-15-oic acid) in two-kidney 1 clip (2K-1C) renal hypertension. Methods: Vascular reactivity experiments were performed in aortic rings isolated from 2K-1C and normotensive (2K) male Wistar rats. Nitrate/nitrite (NOx) measurement was performed in aortas by colorimetric assay. Blood pressure measurements were performed in conscious rats. Results: Labda-15-oic acid (0.1-300 µmol/l) and forskolin (0.1 nmol/l - 1 µmol/l) relaxed endothelium-intact and endothelium-denuded aortas from both 2K-1C and 2K rats. Labda-15-oic acid was more effective at inducing relaxation in endothelium-intact aortas from 2K pre-contracted with phenylephrine when compared to the endothelium-denuded ones. Forskolin was more potent than labda-15-oic acid at inducing vascular relaxation in arteries from both 2K and 2K-1C rats. Labda-15-oic acid-induced increase in NOx levels was lower in arteries from 2K-1C rats when compared to 2K rats. Intravenous administration of labda-15-oic acid (0.3-3 mg/kg) or forskolin (0.1-1 mg/kg) induced hypotension in conscious 2K-1C and 2K rats. Conclusion: The present findings show that labda-15-oic acid induces vascular relaxation and hypotension in hypertensive rats.

Interaction of avirulent Leishmania species with rat peritoneal macrophages

An "in vitro" system has been developed for study of host cell-parasite interaction in visceral and cutaneous leishmaniasis. Avirulent promastigotes of L. brasiliensis and L. donovani, from strains originally isolated from human cases and mantained by serial culture in Davis' Medium were allowed to infect cultured macrophages from rat peritoneal exudate. Challenge of the macrophages by parasites took place in 199 medium, at 33ºC for L. brasiliensis and at 37ºC for L. donovani. Although the rat is resistant to infections by Leishmania spp., the promastigotes not only invaded the host cells, but transformed into amastigotes and later mutiplied, from 10 min after challenge to 24 hours later.

Enterolobin induces rat paw oedema independently of PAF-acether

The potential participation of PAF-acether (PAF) on the paw oedema triggered by enterolobin was investigated. Intraplantar injections of enterolobin )5-20 µg/paw) yielded a dose response curve for edema which appeared after 30 min, peaked in the interval between 2-4 h and faded after 24h. The pre-treatment with BN 52021, but not with other PAF antagonists such as PCA 4248 or WEB 2086, significantly blocked enterolobin-induced oedema. To clarify better the discrepant results obtained with the PAF antagonists, desensitization to PAF was performed. The oedema triggered by enterolobin was not modified in paf desensitized animals. It was concluded that the paw inflammation induced by enterolobin does not require PAF mechanism.

Induction of synthesis of the rat cystatin S protein by the submandibular gland during the acute phase of experimental Chagas disease

Rats experimentally infected with Trypanosoma cruzi Y strain exhibited hypertrophy of the submandibular gland at 18 days after infection.SDS-PAGE of infected rats saliva revealed the presence of an additional band with an apparent molecular weight of about 13KDa. Electrophoresis of protein salivaand immunochemical analysis with antibody against rat cystatin S confirmed that the protein was identical to that induced by beta adrenergic stimulation.

Effect of selective phosphodiesterase inhibitors on the rat eosinophil chemotactic response in vitro

In the present study, we have performed a comparative analysis of the effect of selective inhibitors of phosphodiesterase (PDE) type III, IV and V on eosinophil chemotaxis triggered by platelet activating factor (PAF) and leukotriene B4 (LTB4) in vitro. The effect of the analogues N6-2'-O-dibutyryladenosine 3':5' cyclic monophosphate (Bt2 cyclic AMP) and N2-2'-O- dibutyrylguanosine 3':5' cyclic monophosphate (Bt2 cyclic GMP) has also been determined. The eosinophils were obtained from the peritoneal cavity of naive Wistar rats and purified in discontinuous Percoll gradients to 85-95% purity. We observed that pre-incubation of eosinophils with the PDE type IV inhibitor rolipram suppressed the chemotactic response triggered by PAF and LTB4, in association with an increase in the intracellular levels of cyclic AMP. In contrast, neither zaprinast (type V inhibitor) nor type III inhibitors milrinone and SK&F 94836 affected the eosinophil migration. Only at the highest concentration tested did the analogue Bt2 cyclic AMP suppress the eosinophil chemotaxis, under conditions where Bt2 cyclic GMP was ineffective. We have concluded that inhibition of PDE IV, but not PDE III or V, was able to block the eosinophil chemotaxis in vitro, suggesting that the suppressive activity of selective PDE IV inhibitors on tissue eosinophil accumulation may, at least, be partially dependent on their ability to directly inhibit the eosinophil migration.

Experimental evidence and ecological perspectives for the adaptation of Schistosoma mansoni Sambon, 1907 (Digenea: Schistosomatidae) to a wild host, the water-rat, Nectomys squamipes Brants, 1827 (Rodentia: Sigmodontinae)

Due to the semi aquatic habits and the overlap of the geographical distribution of the water-rat, Nectomys spp., with schistosomiasis endemic areas, these wild rodents are very likely to acquire Schistosoma mansoni infection in their daily activities. The role of the water-rat in the S. mansoni cycle would be substantiated if one could prove that these rodents acquire the parasite during their own activity time, a completely independent time schedule of human activities. To pursue this goal, we performed two field experiments in the municipality of Sumidouro, State of Rio de Janeiro, Brazil, a schistosomiasis endemic area where N. squamipes is found naturally infected. One experiment was devised as a series of observations of activity time of the water-rat. The other experiment was a test of the occurrence of late transmission of S. mansoni to the water-rat. The daily activity pattern showed that the water-rat is active chiefly just after sunset. At both diurnal and late exposition essays the water-rat sentinels got infected by S. mansoni. These findings clarify ecological and behavioral components necessary to the adaptation of S. mansoni to the water-rat as a non human definitive host and the existence of a transmission cycle involving this animals as a reservoir.

Hypertensive portal colopathy in schistosomiasis mansoni: proposal for a classification

Portal hypertension is a frequent complication of chronic liver disease, detected not only in schistosomiasis, but also in cirrhosis of any etiology. Vascular alterations in the colonic mucosa are a potential source for acute or chronic bleeding and have been observed in patients with portal hypertension. The purpose of this prospective study was to describe and propose a classification for the vascular alterations of portal hypertension in the colonic mucosa among patients with hepatosplenic schistosomiasis mansoni. One or more alterations of portal colopathy were observed in all patients and they were classified according to their intensity, obeying the classification proposed by the authors. Portal colopathy is an important finding in hepatosplenic schistosomiasis and might be the cause of lower gastrointestinal bleeding in patients with severe portal hypertension.

Participation of cytokines in the necrotic-inflammatory lesions in the heart and skeletal muscles of Calomys callosus infected with Trypanosoma cruzi

Calomys callosus, a sylvatic reservoir of Trypanosoma cruzi, when infected with the Colombian strain (Biodeme Type III, T. cruzi I ) develops necrotic-inflammatory lesions and intense early fibrogenesis in the heart and skeletal muscles, that spontaneously regress. Participation of pro-inflammatory and pro-fibrogenic cytokines, such as tumor necrosis factor-alpha (TNF-alpha), gamma interferon (IFN-gamma) , and tumor growth factor-beta (TGF-beta), in the pathogenesis of the lesions is herein studied. Eighty C. callosus weighing 20 to 30 g were used. Seventy of them were inoculated with the Colombian strain (10(5) blood forms) and 10 were maintained as intact non-infected controls. After infection, C. callosus were sacrificed at different time-points from 15 to 70 days. The heart and skeletal muscle were processed for histopathology and cryopreserved for immunohistochemistry. Early necrotic lesions of parasitized skeletal muscle and myocardium with intense inflammatory lesions were present. Search for the in situ presence of TNF-alpha and IFN-gamma, was performed using rat-IgG anti-mouse antibodies against these cytokines. For the in situ search of TGF-beta, rabbit IgG anti-mouse antibodies were used. Immunolabeling of the cytokines in tissues of infected C. callosus was successful. The cytokines TNF-alpha, IFN-gamma , and TGF-beta were detected in the cytoplasm of macrophages and in the necrotic material from 15 to 45 days post-infection, decreasing their intensity until complete disappearance by the 65th day, which correlated with subsiding histopathological lesions. These findings suggest the participation of these cytokines in the control of parasite multiplication, in the development of an early fibrogenesis and in the regression of fibrotic-inflammatory lesions observed in C. callosus.

An ecological field study of the water-rat Nectomys squamipes as a wild reservoir indicator of Schistosoma mansoni transmission in an endemic area

Small mammals are found naturally infected by Schistosoma mansoni, becoming a confounding factor for control programs of schistosomiasis in endemic areas. The aims of this study were: to investigate the infection rates by S. mansoni on the water-rat Nectomys squamipes during four years in endemic areas of Sumidouro, state of Rio de Janeiro, using mark-recapture technique; to compare two diagnostic methods for schistosomiasis; and to evaluate the effects of the chemotherapy in the human infected population on the rodent infection rates. The rodent infection rates of S. mansoni increased when rodent population sizes were lower. Coprology and serology results presented the same trends along time and were correlated. Serology could detect recent infection, including the false negatives in the coprology. The chemotherapy in the humans could not interrupt the rodent infection. Rodents can increase the schistosomiaisis transmission where it already exists, they probably maintain the transmission cycle in the nature and can be considered as biological indicators of the transmission sites of this parasite since they are highly susceptible to infection. The water-rats may present different levels of importance in the transmission dynamics of S. mansoni infection cycle for each area, and can be considered important wild-reservoirs of this human disease.

Benznidazole biotransformation in rat heart microsomal fraction without observable ultrastructural alterations: comparison to Nifurtimox-induced cardiac effects

Benznidazole (Bz) and Nifurtimox (Nfx) have been used to treat Chagas disease. As recent studies have de-monstrated cardiotoxic effects of Nfx, we attempted to determine whether Bz behaves similarly. Bz reached the heart tissue of male rats after intragastric administration. No cytosolic Bz nitroreductases were detected, although microsomal NADPH-dependent Bz nitroreductase activity was observed, and appeared to be mediated by P450 reductase. No ultrastructurally observable deleterious effects of Bz were detected, in contrast to the overt cardiac effects previously reported for Nfx. In conclusion, when these drugs are used in chagasic patients, Bz may pose a lesser risk to heart function than Nfx when any cardiopathy is present.

Larval recovery of Toxocara cati in experimentally infected Rattus norvegicus and analysis of the rat as potential reservoir for this ascarid

Toxocara cati is a common feline parasite transmitted by the ingestion of embryonated eggs, by the transmammary route or by predation of paratenic hosts harbouring third-stage larvae in their bodies. In the present study, the larval distribution of T. cati in tissues and organs of Rattus norvegicus experimentally infected with 300 embryonated eggs was analysed. Third-stage larvae were recovered from livers, lungs, kidneys, eyes, brains and carcasses of infected rats, following tissue digestion with HCl 0.5% for 24 h at 37°C. Some differences from the known larval distribution of Toxocara canisin the same rodent species were found.

Infection in a rat model reactivates attenuated virulence after long-term axenic culture of Acanthamoeba spp

Prolonged culturing of many microorganisms leads to the loss of virulence and a reduction of their infective capacity. However, little is known about the changes in the pathogenic strains of Acanthamoeba after long culture periods. Our study evaluated the effect of prolonged culturing on the invasiveness of different isolates of Acanthamoeba in an in vivo rat model. ATCC strains of Acanthamoeba, isolates from the environment and clinical cases were evaluated. The in vivo model was effective in establishing the infection and differentiating the pathogenicity of the isolates and re-isolates. The amoebae cultured in the laboratory for long periods were less virulent than those that were recently isolated, confirming the importance of passing Acanthamoeba strains in animal models.