Exposição perinatal ao chumbo e desnutrição intra-uterina, isoladamente ou em associação: efeitos cardiovasculares em ratos recém-desmamados

Plumbism is considered the oldest occupational disease. Among the pathophysiological effects associated with lead (Pb) are cardiovascular disorders. Many diseases that develop later in life are determined during the early stages of life, under the influence of exposure and preferred diet of the mother. Still, one should consider that many environmental contaminants at levels not harmful can determine pathophysiological processes if physical or chemical stressors and/or pathological conditions are present. In this context, the intrauterine malnutrition may represent an additional risk factor in exposure to Pb during pregnancy and lactation. For these reasons, the objective of this study was to evaluate the cardiovascular risk of weaned rats that have suffered perinatal exposure to Pb and intrauterine malnutrition, alone or in combination. After mating, female rats were divided into control (ctrl, ad libitum), food restriction (RA, the same diet 50% of consumption in the control group during pregnancy), exposed to Pb (500 ppm Pb in drinking water during pregnancy and lactation) and association (As, received the last two procedures in combination). Cumulative concentration-effect curves (CECs) to CaCl2 and noradrenaline (NA) were obtained in rings with and without endothelium of the same thoracic aorta from male weaned rats (23-25 days old). Maternal weight, litter weight, weight and number of pups at birth, anogenital distance, arterial blood pressure (ABP) and weight of tissues (kidney, liver, aorta, left ventricle) were evaluated. Changes in vascular reactivity were assessed by the maximum response (MR) and 50% effective concentration (EC50). Data were presented as mean ± SEM. Statistical analysis was performed by multifactorial analysis of variance and Tukey's post test. Body weight of dams did not differ between the experimental groups, except on the...(Complete abstract click electronic access below)

O Wortmannin reverte a hiporreatividade de aortas à fenilefrina associada à fase final da prenhez de ratas espontaneamente hipertensas (SHR)

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

Stress vulnerability during adolescence

Objective: This study investigated the physiological and somatic changes evoked by daily exposure to the same type of stressor (homotypic) or different aversive stressor stimuli (heterotypic) in adolescent and adult rats, with a focus on cardiovascular function. The long-term effects of stress exposure during adolescence were also investigated longitudinally. Methods: Male Wistar rats were exposed to repeated restraint stress (RRS, homotypic) or chronic variable stress (CVS, heterotypic). Results: Adrenal hypertrophy, thymus involution, and elevated plasma glucocorticoid were observed only in adolescent animals, whereas reduction in body weight was caused by both stress regimens in adults. CVS increased mean arterial pressure (adolescent: p = .001; adult: p = .005) and heart rate (HR; adolescent: p = .020; adult: p = .011) regardless of the age, whereas RRS increased blood pressure selectively in adults (p = .001). Rest tachycardia evoked by CVS was associated with increased cardiac sympathetic activity in adults, whereas a decreased cardiac parasympathetic activity was observed in adolescent animals. Changes in cardiovascular function and cardiac autonomic activity evoked by both CVS and RRS were followed by alterations in baroreflex activity and vascular reactivity to vasoconstrictor and vasodilator agents in adolescent adult animals. Except for the circulating glucocorticoid change, all alterations observed during adolescence were reversed in adulthood. Conclusions: These findings suggest a stress vulnerability of adolescents to somatic and neuroendocrine effects regardless of stress regimen. Our results indicated an age-stress type-specific influence in stress-evoked cardiovascular/autonomic changes. Data suggest minimal consequences in adulthood of stress during adolescence.

Papel das espécies reativas de oxigênio na hiporreatividade de aortas à fenilefrina observada no final da prenhez de Ratas Espontaneamente Hipertensas (SHR)

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Stress vulnerability during adolescence: comparison of chronic stressors in adolescent and adult rats

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

Adolescent vulnerability to cardiovascular consequences of chronic social stress: Immediate and long-term effects of social isolation during adolescence

It has been demonstrated that disruption of social bonds and perceived isolation (loneliness) are associated with an increased risk of cardiovascular morbidity and mortality. Adolescence is proposed as a period of vulnerability to stress. Nevertheless, the impact of chronic social stress during this ontogenic period in cardiovascular function is poorly understood. Therefore, the purpose of this study was to compare the impact in cardiovascular function of social isolation for 3 weeks in adolescent and adult male rats. Also, the long-term effects of social isolation during adolescence were investigated longitudinally. Social isolation reduced body weight in adolescent, but not in adult animals. Disruption of social bonds during adolescence increased arterial pressure without affecting heart rate and pulse pressure (PP). Nevertheless, social isolation in adulthood reduced systolic arterial pressure and increased diastolic arterial pressure, which in turn decreased PP without affecting mean arterial pressure. Cardiovascular changes in adolescents, but not adults, were followed by facilitation of both baroreflex sensitivity and vascular reactivity to the vasodilator agent acetylcholine. Vascular responsiveness to either the vasodilator agent sodium nitroprusside or the vasoconstrictor agent phenylephrine was not affected by social isolation. Except for the changes in body weight and baroreflex sensitivity, all alterations evoked by social isolation during adolescence were reversed in adulthood after moving animals from isolated to collective housing. These findings suggest a vulnerability of adolescents to the effects of chronic social isolation in cardiovascular function. However, results indicate minimal cardiovascular consequences in adulthood of disruption of social bonds during adolescence. © 2015 Wiley Periodicals, Inc. Develop Neurobiol, 2015.

A possible increase of activity of endothelial l-arginine/nitric oxide pathway in aortas of diet-induced obesity rats

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

Vascular endothelial growth factor (VEGF) and VEGF-receptor expression in placenta of hyperglycemic pregnant women

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

Effects of diethylpropion treatment and withdrawal on aorta reactivity, endothelial factors and rat behavior

Diethylpropion (DEP) is an amphetamine-like compound used as a coadjutant in the treatment of obesity and which presents toxicological importance as a drug of abuse. This drug causes important behavioral and cardiovascular complications; however, the vascular and behavioral alterations during DEP treatment and withdrawal, have not been determined. We evaluated the effects of DEP treatment and withdrawal on the rat aorta reactivity to noradrenaline, focusing on the endothelium, and the rat behavior during DEP treatment and withdrawal. DEP treatment caused a hyporreactivity to noradrenaline in aorta, reversible after 2 days of withdrawal and abolished by both the endothelium removal and the presence of L-NAME, but not by the presence of indomethacin. Furthermore, DEP treatment increased the general activity of rats. Contrarily, DEP withdrawal caused a decrease in the locomotor activity and an increase in grooming behavior, on the 2nd and 7th days after the interruption of the treatment, respectively. DEP treatment also caused an adaptive vascular response to noradrenaline that seems to be dependent on the increase in the endothelial nitric oxide system activity, but independent of prostaglandins synthesis. The data evidenced chronological differences in the adaptive responses of the vascular and central nervous systems induced by DEP treatment. Finally, a reversion of the adaptive response to DEP was observed in the vascular system during withdrawal, whereas a neuroadaptive process was still present in the central nervous system post-DEP. These findings advance on the understanding of the vascular and behavioral pathophysiological processes involved in the therapeutic and abusive uses of DEP. (C) 2003 Elsevier B.V. (USA). All rights reserved.

Vascular effects of long-term propranolol administration after chronic nitric oxide blockade

Long-term propranolol treatment reduces arterial blood pressure in hypertensive individuals mainly by reducing peripheral vascular resistance, but mechanisms underlying their vasodilatory effect remain poorly investigated. This study aimed to investigate whether long-term propranolol administration ameliorates the impairment of relaxing responses of aorta and mesenteric artery from rats made hypertensive by chronic nitric oxide (NO) deficiency, and underlying mechanisms mediating this phenomenon. Male Wistar rats were treated with N-omega-Nitro-L-arginine methyl ester (L-NAME; 20 mg/rat/day) for four weeks. DL-Propranolol (30 mg/rat/day) was given concomitantly to L-NAME in the drinking water. Treatment with L-NAME markedly increased blood pressure, an effect largely attenuated by DL-propranolol. In phenylephrine-precontracted aortic rings, the reduction of relaxing responses for acetylcholine (0.001-10 mu M) in L-NAME group was not modified by DL-propranolol, whereas in mesenteric rings the impairment of acetylcholine-induced relaxation by L-NAME was significantly attenuated by DL-propranolol. In mesenteric rings precontracted with KCl (80 MM), DL-propranolol failed to attenuate the impairment of acetylcholine-induced relaxation by L-NAME. The contractile responses to extracellular CaCl2 (1-10 mM) were increased in L-NAME group, and co-treatment with DL-propranolol reduced this response in both preparations in most Ca2+ concentrations used. The NO2/NO3 plasma levels and superoxide dismutase (SOD) activity were reduced in L-NAME-treated rats, both of which were significantly prevented by DL-propranolol. In conclusion, propranolol-induced amplification of the relaxation to acetylcholine in mesenteric arteries from L-NAME-treated rats is sensitive to depolarization. Additional mechanisms involving blockade of Ca2+ entry in the vascular smooth muscle and increase in NO bioavailability contributes to beneficial effects of long-term propranolol treatment. (C) 2007 Elsevier B.V. All rights reserved.

Effect of NωNLA or dexamethasone on vascular hyporeactivity induced by E. coli endotoxin in sham and adrenalectomized rats

Induction of iNOS by bacterial products is considered to be part of the defense mechanism against infection. However, it has been suggested that the bacterial-induced NO-overproduction may be involved in the vascular hyporeactivity and in septic shock. It is well known that glucocorticoids prevent the induction of iNOS by Etx in rats. In the present study, dexamethasone diminished but not abolished Etx-induced vascular hyporeactivity in rats. Our results showed that the inhibition of iNOS protects sham rats against the lethal shock produced by Etx, but, in Adx rats, the NωNLA, an iNOS inhibitor, did not reduce Etx-induced mortality. Interestingly, the lack of glucocorticoid impaired the protective effect of NωNLA against Etx-induced hyporeactivity and shock in rats. A conceivable pharmacological approach to protect tissues against deleterious effect of excessive NO production includes inhibition of the iNOS, because the absence of glucocorticoid may increase the iNOS gene expression, with NO-overproduction induced by Etx, suggesting that the glucocorticoids might be of therapeutic value for the treatment of hyporeactivity and shock triggered by sepsis.

Structural and Biochemical Characterization of Peroxiredoxin Q beta from Xylella fastidiosa CATALYTIC MECHANISM and HIGH REACTIVITY

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

Renal and vascular effects of the natriuretic peptide isolated from Crotalus durissus cascavella venom

Crotalus durissus cascavella is a snake that is usually found in the scrublands of northeast Brazil. The components of its venom may have effects on the vascular and renal systems. Recently, a new bradykinin inhibitory peptide has been identified in the venom of the Crotalinae family. The aim of the present study was to investigate the renal and vascular effects of the natriuretic peptide isolated from the venom of Crotalus durissus cascavella (NP2_Casca). The chromatographic profile showed the fractionation of substances identified as convulxin, gyroxin, crotoxin and crotamine, as well as fractions V and VI. The electrophoretic profile of fraction V consisted of several bands ranging from approximately 6 kDa to 13 kDa, while fraction VI showed only two main electrophoretic bands with molecular weights of approximately 6 and 14 kDa. Reverse-phase chromatography showed that NP2_Casca corresponds to about 18% of fraction VI and that this fraction is the main natriuretic peptide. NP2_Casca was compared to other natriuretic peptides from other sources of snake venom. All amino acid sequences that were compared showed a consensus region of XGCFGX, XLDRIX and XSGLGCX. The group treated with NP2-Casca showed an increase in perfusion pressure, renal vascular resistance, urinary flow and glomerular filtration rate. The percent of total and proximal tubular transport of sodium was reduced significantly after administration of the peptide. The mean arterial pressure showed a dose-dependent decrease after infusion of NP2_Casca, and an increase in nitrite production. In the aortic ring assay, NP2_Casca caused a relaxant effect in endothelium-intact thoracic aortic rings precontracted with phenylephrine in the presence and absence of isatin. NP2_Casca failed to relax the aortic rings precontracted with an isosmotic potassium Krebs-Henseleit solution. In conclusion, the natriuretic peptide isolated from Crotalus durissus cascavella venom produced renal and vascular effects. NP2_Casca reduced total and proximal sodium tubular transport, leading to an increase in sodium excretion, thereby demonstrating a diuretic action. A hypotensive effect was displayed in an arterial pressure assay, with an increase in nitrite production, suggesting a possible vasoactive action. (C) 2008 Elsevier Ltd. All rights reserved.

Renal- and calcium-dependent vascular effects of Polybia paulista wasp venom

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Reactivity of p53 protein in canine transmissible venereal tumor

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