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Low-level laser therapy (LLLT) has been used as an anti-inflammatory treatment in several disease conditions, even when inflammation is a secondary consequence, such as in myocardial infarction (MI). However, the mechanism by which LLLT is able to protect the remaining myocardium remains unclear. The present study tested the hypothesis that LLLT reduces inflammation after acute MI in female rats and ameliorates cardiac function. The potential participation of the Renin-Angiotensin System (RAS) and Kallikrein-Kinin System (KKS) vasoactive peptides was also evaluated. LLLT treatment effectively reduced MI size, attenuated the systolic dysfunction after MI, and decreased the myocardial mRNA expression of interleukin-1 beta and interleukin-6 in comparison to the non-irradiated rat tissue. In addition, LLLT treatment increased protein and mRNA levels of the Mas receptor, the mRNA expression of kinin B2 receptors and the circulating levels of plasma kallikrein compared to non-treated post-MI rats. On the other hand, the kinin B1 receptor mRNA expression decreased after LLLT. No significant changes were found in the expression of vascular endothelial growth factor (VEGF) in the myocardial remote area between laser-irradiated and non-irradiated post-MI rats. Capillaries density also remained similar between these two experimental groups. The mRNA expression of the inducible nitric oxide synthase (iNOS) was increased three days after MI, however, this effect was blunted by LLLT. Moreover, endothelial NOS mRNA content increased after LLLT. Plasma nitric oxide metabolites (NOx) concentration was increased three days after MI in non-treated rats and increased even further by LLLT treatment. Our data suggest that LLLT diminishes the acute inflammation in the myocardium, reduces infarct size and attenuates left ventricle dysfunction post-MI and increases vasoactive peptides expression and nitric oxide (NO) generation. [ABSTRACT FROM AUTHOR]

Sympathetic hyperactivity induces adverse effects in myocardial. Recent studies have shown that exercise training induces cardioprotection against sympathetic overload; however, relevant mechanisms of this issue remain unclear. We analyzed whether exercise can prevent pathological hypertrophy induced by sympathetic hyperactivity with modulation of the kallikrein-kinin and angiogenesis pathways. Male Wistar rats were assigned to non-trained group that received vehicle; non-trained isoproterenol treated group (Iso, 0.3 mg kg−1 day−1); and trained group (Iso+Exe) which was subjected to sympathetic hyperactivity with isoproterenol. The Iso rats showed hypertrophy and myocardial dysfunction with reduced force development and relaxation of muscle. The isoproterenol induced severe fibrosis, apoptosis and reduced myocardial capillary. Interestingly, exercise blunted hypertrophy, myocardial dysfunction, fibrosis, apoptosis and capillary decreases. The sympathetic hyperactivity was associated with high abundance of ANF mRNA and β-MHC mRNA, which was significantly attenuated by exercise. The tissue kallikrein was augmented in the Iso+Exe group, and kinin B1 receptor mRNA was increased in the Iso group. Moreover, exercise induced an increase of kinin B2 receptor mRNA in myocardial. The myocardial content of eNOS, VEGF, VEGF receptor 2, pAkt and Bcl-2 were increased in the Iso+Exe group. Likewise, increased expression of pro-apoptotic Bad in the Iso rats was prevented by prior exercise. Our results represent the first demonstration that exercise can modulate kallikrein-kinin and angiogenesis pathways in the myocardial on sympathetic hyperactivity. These findings suggest that kallikrein-kinin and angiogenesis may have a key role in protecting the heart. [ABSTRACT FROM AUTHOR]

Alterations in transforming growth factor (TGF)-β signalling have been frequently implicated in human cancer, and an important mechanism underlying its pro-oncogenic nature is suppression of the host antitumour immune response. Considering the immunosuppressive effect of TGF-β, we asked whether human tumour cells, known to secrete TGF-β in culture, would survive and grow when implanted into the peritoneal cavity of immunocompetent mice. Therefore, we developed a xenogeneic model where mice were intraperitoneally (i.p.) injected with a TGF-β-secreting human colorectal adenocarcinoma cell line, LISP-A10. Although animals did not develop macroscopic tumours, the recovery and isolation of human tumour cells was achieved when an inflammatory environment was locally induced by the administration of complete Freund's adjuvant (CFA). This procedure significantly increased TGF-β concentrations in the peritoneal fluid and was accompanied by impaired activation of the host-specific immune response against LISP-A10 cells. Furthermore, inflammatory lesions resembling human inflammatory pseudotumours (IPTs) were observed on the surface of i.p. organs. These lesions could be induced by either injection of LISP-A10 cells, cells-conditioned medium or recombinant TGF-β but only after administration of CFA. In addition, host cyclooxygenase-2 and kinin receptors played an important role in the induction of TGF-β-mediated IPT-like lesions in our experimental model. [ABSTRACT FROM AUTHOR]

Kinins, a special class of polypeptides, are represented by bradykinin (BK), kallidin (Lys-BK), as well as their metabolites. The biological actions of these polypeptides binding on their receptors (B1 and B2) have been related to inflammation process, cytokines action, glutamate release and prostaglandins production. Usually, kinin B1 receptor is not expressed at a significant level under physiologic conditions in most tissues, but its expression is induced by injury, or upon exposure in vivo or in vitro to pro-inflammatory mediators. The kinin B2 receptor subtype is constitutively and widely expressed throughout the central and peripheral nervous system. These data raise the possibility for de novo expression of those receptors during the temporal lobe epilepsy (TLE), which has been related to cell death, gliosis and hippocampal reorganization. To correlate kinin system and TLE, adult male Wistar rats were submitted to pilocarpine model of epilepsy. The hippocampi were removed 6 h, 5 and 60 days after status epilepticus (SE) onset. The collected tissues were used to study the expression of kinin B1 and B2 mRNA receptors, using Real-Time PCR. Immunohistochemistry assay was also employed to visualize kinin B1 and B2 distribution in the hippocampus. The results show increased kinin B1 and B2 mRNA levels during acute, silent and chronic periods and changes in the kinin B1 and B2 receptors distribution. In addition, the immunoreactivity against kinin B1 receptor was increased mainly during the silent period, where neuron clusters of could be visualized. The kinin B2 receptor immunoreactivity also showed augmentation but mainly during the acute and silent periods. Our results suggest that kinin B1 and B2 receptors play an important role in the epileptic phenomena. [Copyright &y& Elsevier]

The present study was undertaken to determine tonin expression and activity in rat heart presenting isoproterenol-induced hypertrophy. Renin, angiotensin-converting enzyme (ACE), and angiotensinogen (AG) expression were also determined. Wistar rats were treated with isoproterenol for 7 days (5 mg·kg[sup -1]·day[sup -1] sc). For untreated animals, the levels of tonin-specific activity in the atrium were 2.6- and 5.5-fold higher than those of the left and right ventricle, respectively. After treatment, the levels of tonin-specific activity increased twofold in the atrium but did not change in the ventricles. Renin expression was not detectable in these structures, and ACE expression levels did not change with treatment. AG expression was detected in the left ventricle at very low levels compared with the atrium and increased significantly only in the hypertrophied atrium (1.8-fold). Tonin mRNA was not detected in the ventricle but was found at low levels in the atrium, which increased after isoproterenol treatment. Our results permit us to conclude that tonin may play a role in the process of heart hypertrophy in the rat. [ABSTRACT FROM AUTHOR]