Clopidogrel, independent of the vascular P2Y(12) receptor, improves arterial function in small mesenteric arteries from Angll-hypertensive rats

The P2Y(12) receptor antagonist clopidogrel blocks platelet aggregation, improves systemic endothelial nitric oxide bioavailability and has anti-inflammatory effects. Since P2Y(12) receptors have been identified in the vasculature, we hypothesized that clopidogrel ameliorates Angll (angiotensin II)-induced vascular functional changes by blockade of P2Y(12) receptors in the vasculature. Male Sprague Dawley rats were infused with Angll (60 ng/min) or vehicle for 14 days. The animals were treated with clopidogrel (10 mg . kg(-1) of body weight . day(-1)) or vehicle. Vascular reactivity was evaluated in second-order mesenteric arteries. Clopidogrel treatment did not change systolic blood pressure [(mmHg) control-vehicle, 117 +/- 7.1 versus control-clopidogrel, 125 +/- 4.2; Angll vehicle, 197 +/- 10.7 versus Angll clopidogrel, 198 +/- 5.2], but it normalized increased phenylephrine-induced vascular contractions [(%KCI) vehicle-treated, 182.2 +/- 18% versus clopidogrel, 133 +/- 14%), as well as impaired vasodilation to acetylcholine [(%) vehicle-treated, 71.7 +/- 2.2 versus clopidogrel, 85.3 +/- 2.8) in Angll-treated animals. Vascular expression of P2Y(12) receptor was determined by Western blot. Pharmacological characterization of vascular P2Y(12) was performed with the P2Y(12) agonist 2-MeS-ADP [2-(methylthio) adenosine 5`-trihydrogen diphosphate trisodium]. Although 2-MeS-ADP induced endothelium-dependent relaxation [(Emax %) = 71 +/- 12%) as well as contractile vascular responses (Emax % = 83 +/- 12%), these actions are not mediated by P2Y(12) receptor activation. 2-MeS-ADP produced similar vascular responses in control and Angll rats. These results indicate potential effects of clopidogrel, such as improvement of hypertension-related vascular functional changes that are not associated with direct actions of clopidogrel in the vasculature, supporting the concept that activated platelets contribute to endothelial dysfunction, possibly via impaired nitric oxide bioavailability.

Coronary reserve impairment prevents the improvement of left ventricular dysfunction and adversely affects the long-term outcome of patients with hypertensive dilated cardiomyopathy

In hypertension, left ventricular (LV) hypertrophy develops as an adaptive mechanism to compensate for increased afterload and thus preserve systolic function. Associated structural changes such as microvascular disease might potentially interfere with this mechanism, producing pathological hypertrophy. A poorer outcome is expected to occur when LV function is put in jeopardy by impaired coronary reserve. The aim of this study was to evaluate the role of coronary reserve in the long-term outcome of patients with hypertensive dilated cardiomyopathy. Between 1996 and 2000, 45 patients, 30 of them male, with 52 +/- 11 years and LV fractional shortening <30% were enrolled and followed until 2006. Coronary flow velocity reserve was assessed by transesophageal Doppler of the left anterior descending coronary artery. Sixteen patients showed >= 10% improvement in LV fractional shortening after 17 +/- 6 months. Coronary reserve was the only variable independently related to this improvement. Total mortality was 38% in 10 years. The Cox model identified coronary reserve (hazard ratio = 0.814; 95% CI = 0.72-0.92), LV mass, low diastolic blood pressure, and male gender as independent predictors of mortality. In hypertensive dilated cardiomyopathy, coronary reserve impairment adversely affects survival, possibly by interfering with the improvement of LV dysfunction. J Am Soc Hypertens 2010;4(1):14-21. (C) 2010 American Society of Hypertension. All rights reserved.

Controle circadiano e homeostático do sono-virgília em pacientes com acidente vascular encefálico e correlações com a qualidade de vida e o nível de atividade física

The cerebral vascular accident is a neurological dysfunction of vascular origin that leds to development of motor sensibility, cognitive, perceptive and language deficits. Despite the fact that the main sleep disorders in stroke patients are well known, it is still necessary to analyze which mechanisms of regulation of sleep and wakefulness are affected. The objective of this study was to evaluate the changes in the circadian and homeostatic control of sleep-wakefulness in stroke patients and the correlations with quality of life and level of physical activity. The study analyzed 22 stroke patients (55± 12 years old) and 24 healthy subjects (57 ±11 years old). The instruments used in this study were questionnaires on sleep quality, daytime sleepiness, quality of life, physical activity level and the actigraphy. The data were analyzed using the Student `t test, Mann-Whitney test, ANOVA and Spearman's correlation tests. The results showed stability in the sleep-wake circadian expression with changes in the amplitude of the rhythm. However, significant changes were found related to the homeostatic component characterized by increased sleep duration, increased latency, fragmented sleep and lower sleep efficiency. Additional data showed decreased quality of sleep and increased daytime sleepiness, as well as decreased quality of life and level of physical activity. The results indicate that the interaction of circadian and homeostatic control of sleep-wake is compromised and the main reason might be because of the homeostatic component and the lower activity level resulting from the brain damage. Thus, further studies may be developed to evaluate whether behavioral interventions such as increased daytime activity and restriction of sleep during the day can influence the homeostatic process and its relation to circadian component, resulting in improved quality of nocturnal sleep in stroke patients

Grau de conhecimento de pacientes sobre o acidente vascular cerebral e a necessidade do uso de cartilha educativa para orientação fisioterapêutica

Stroke is a neurological dysfunction of vascular origin that causes physical impairments and disabilities. Brazil leads the statistics stroke mortality among Latin American countries, demonstrating still be a neglected disease in this country. The incidence is related to risk factors and still is great misinformation in our country about stroke, treatment and prophylaxis. The aim of this study was to assess the degree of knowledge about stroke and patients need to use educational booklet for physiotherapy. The sample consisted of 53 patients, 22 females and 31 males, mean age 56.2 ± 10.9 years. Patients were evaluated by completing questionnaires, observing the socio-demographic and clinical aspects, neurological assessment, functional assessment, knowledge of pathology and presenting educational booklet. The data were analyzed using the chi-square test. According to the results, it was observed that the patients had not enough knowledge about the terminology, complications and warning signs of stroke, were not aware and did not perform the proper positioning of the limb and transfers, however, were aware and performed the stretching maneuvers. This reveals the need to implement policies that lead to information about stroke population. Following discharge from outpatient physical therapy using educational booklets with guidelines on positioning, stretching exercises and transfer is important in functional rehabilitation and encouraging independence of the individual affected by stroke

Qualidade subjetiva do sono e queixa de insônia em pacientes com Acidente Vascular Cerebral

Brain injury can be associated with changes in the sleep-wake cycle. However, studies about sleep disturbances and their relationship with quality of sleep are scarce. Besides, it remains to be known how stroke affects the mechanisms of sleep. The aim of this study was to investigate quality of sleep, complaints of sleep disturbances and associated factors in stroke patients from the Physical Therapy services in Natal -RN. This was a cross-sectional descriptive study involving 70 individuals (aged 45-65 years), 40 patients (57 ± 7 years), 11 ± 9 months after injury, and 30 healthy individua ls (52 ± 6 years), evaluated with the Pittsburgh Sleep Quality Index (PSQI) and Sleep Habits Questionnaire. The data were analyzed by Chi-square test, t Student test and logistic regression. Poor quality sleep was found in 57,5% of the patients (6,3 ± 3,5) and was significantly higher than in the control population (3,9 ± 2,2) (t Student test, p=0,002). The patients showed significantly higher value of PSQI than controls: sleep latency (p=0,019), length of sleep (p=0,039) and dysfunction during the day (p=0,001). Regarding complaints of sleep disturbances (dyssomnias and parasomnias) analyzed by Chi-square test, the complaint of insomnia was the most prevalent (patients: 37,5%; healthy subjects: 6,7%; p=0,007). Regression analysis showed that sl eep latency (p=0,036) and complaint of insomnia (p=0,036) were associated with quality sleep. In addition, female gender (p=0,036) and complaint of broken sleep (p=0,003) were considered risk factors for the presence of insomnia. Our results show that stroke affects the homeostatic process of sleep. Shorter sleep latency and the absence of insomnia are considered protective factors for good sleep quality and this should be taken into consideration in the diagnostic and therapeutic strategies

Oxidative stress and inflammatory mediators contribute to endothelial dysfunction in high-fat diet-induced obesity in mice

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

Role of Peritubular Capillaries and Vascular Endothelial Growth Factor in Chronic Allograft Nephropathy

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

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.

Upregulation of gp91(phox) Subunit of NAD(P)H Oxidase Contributes to Erectile Dysfunction Caused by Long-term Nitric Oxide Inhibition in Rats: Reversion by Regular Physical Training

OBJECTIVES To test the hypothesis that glyco protein 91phox (gp91(phox)) subunit of nicotinamide adenine dinucleotide phosphate [NAD(P) H] oxidase is a fundamental target for physical activity to ameliorate erectile dysfunction (ED). Vascular risk factors are reported to contribute to ED. Regular physical exercise prevents cardiovascular diseases by increasing nitric oxide (NO) production and/or decreasing NO inactivation.METHODS Male Wistar rats received the NO synthesis inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME) for 4 weeks, after which animals were submitted to a run training program for another 4 weeks. Erectile functions were evaluated by in vitro cavernosal relaxations and intracavernous pressure measurements. Expressions of gp91(phox) subunit and neuronal nitric oxidase synthase in erectile tissue, as well as superoxide dismutase activity and nitrite/nitrate (NO(x)) levels were determined.RESULTS The in vitro acetylcholine-and electrical field stimulation-induced cavernosal relaxations, as well as the increases in intracavernous pressure were markedly reduced in sedentary rats treated with L-NAME. Run training significantly restored the impaired cavernosal relaxations. No alterations in the neuronal nitric oxidase synthase protein expression (and its variant penile neuronal nitric oxidase synthase) were detected. A reduction of NO(x) levels and superoxide dismutase activity was observed in L-NAME-treated animals, which was significantly reversed by physical training. Gene expression of subunit gp91(phox) was enhanced by approximately 2-fold in erectile tissue of L-NAME-treated rats, and that was restored to basal levels by run training.CONCLUSIONS Our study shows that ED seen after long-term L-NAME treatment is associated with gp91(phox) subunit upregulation and decreased NO bioavailability. Exercise training reverses the increased oxidative stress in NO-deficient rats, ameliorating the ED. UROLOGY 75: 961-967, 2010. (C) 2009 Elsevier B.V.

Análise cinemática da marcha em indivíduos com Acidente Vascular Encefálico

Introduction. Gait becomes the individual independence for their daily activities. The functional deficit caused by central lesion as stroke, makes difficult this motor independence, mainly the locomotion. Objective. Analyze the kinematics gait in stroke patients. Method. It was included 8 patients with clinical diagnosis of stroke, 4 with hemiparesia on the right and 4 on the left. It was analyzed gait spatial-temporal parameters as: length, duration and average speed of the step, using the register in videotape and the software of image 6.3 Dvideow Barros. Results. All patients presented alterations in the kinematics standards of the gait, with lesser duration and length of step, and greater speed than normal subjects. Conclusion. The motor disorder caused by the central lesions produces alterations in the kinematics standards of the gait, in order to adapt the neuro-sensorial sequels, the demands of the task and the way where they live.

Percepção da imagem corporal de adultos após acidente vascular encefálico: uma abordagem psicofísica

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Avaliação vascular não invasiva (NIVA) em gestantes com diabete gestacional e com hiperglicemia leve utilizando o SphygmoCor

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Efeitos da exposição à sílica sobre a responsividade vascular e de vias aéreas de ratos

Silicosis, a common type of pneumoconiosis, is an occupational lung disease caused by inhalation of silica dust often with mining activity and thus reaches the miners. The fine and ultrafine silica particles deposited in the alveolar epithelium may lead to the development of progressive massive fibrosis. An increased reactive oxygen species (ROS) production has been proposed to explain the mechanism for induction of pulmonary fibrosis in silicosis. In this situation, alveolar macrophages are activated to phagocytes silica particles deposited in the alveoli. The activated macrophages secrete large amounts of ROS that in turn induce synthesis of fibrotic factors. In addition, the activity of antioxidant enzymes is impaired, which results in increased lipid peroxidation, as well as generating a local inflammatory process. Diffuse pulmonary fibrosis progresses with interstitial collagen deposition. Interstitial collagen overlies small pulmonary arteries and arterioles and thus it is associated with pulmonary hypertension in pulmonary fibrotic diseases. In addition, cytokines and silica particles passing through the respiratory membrane can reach the bloodstream. In this context, the increase in the generation of ROS in the circulation may lead to a reduction in the bioavailability of nitric oxide, an important endothelium-derived relaxing factor. A deficiency in the nitric oxide bioavailability can result in vascular endothelial dysfunction. Moreover, pro-inflammatory cytokines could contribute to the impairment of endothelial function. In the airways, pro-inflammatory cytokines can reduce the smooth muscle responsiveness to β- adrenergic agonists as isoproterenol. Thus, the aim of this study was to evaluate the effect of silica dust instillation in the function of the pulmonary artery, aorta and trachea of rats with acute silicosis. For this purpose, male Wistar rats were anesthetized... (Complete abstract click electronic access below)

Chronic stress improves NO- and Ca2+flux-dependent vascular function: a pharmacological study

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

Efeito do treinamento físico aeróbio na reatividade vascular da artéria ilíaca em camundongos LDL-/-

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)