RESUMO
1. This study investigates the time course of pulmonary arterial hypertension (PAH) due to monocrotaline (MCT) and its association with cardiac function and oxidative stress markers in the left ventricle (LV). 2. Male Wistar rats were divided into six groups: 7 days, 21 days, and 31 days for both control and MCT groups. Following echocardiographic analysis, the heart was removed. The LV was separated and homogenized to analyze oxidized-to-total glutathione ratio and thioredoxin reductase (TrxR) activity as well as hydrogen peroxide (H(2) O(2) ) and ascorbic acid levels. 3. There was significant (P < 0.01) cardiac and right ventricle (RV) hypertrophy and pulmonary congestion in the MCT 21 day and 31 day groups. Echocardiography showed a change in the flow wave of the pulmonary artery at 21 days after MCT treatment. There was an increase in the LV ejection time (P < 0.05) at 31 days after MCT. The LV H(2)O(2) concentration was increased (P < 0.05) in the MCT 21 day and MCT 31 day groups compared with controls. There was a reduction (P < 0.05) in the LV ascorbic acid concentration and an increase (P < 0.05) in TrxR activity in the MCT 31 day rats. 4. Our findings showed RV changes due to pulmonary hypertension at 21 days after MCT injection. There was a correlation between the degree of dysfunction and the morphometry of the heart chambers, along with impairment of the antioxidant/pro-oxidant balance in the LV 31 days after the beginning of the protocol. This study suggests that LV changes follow RV dysfunction subsequent to pulmonary hypertension.
Assuntos
Ventrículos do Coração/química , Ventrículos do Coração/fisiopatologia , Hipertensão Pulmonar/metabolismo , Hipertensão Pulmonar/fisiopatologia , Estresse Oxidativo/fisiologia , Animais , Ácido Ascórbico/análise , Cardiomegalia/diagnóstico por imagem , Cardiomegalia/fisiopatologia , Hipertensão Pulmonar Primária Familiar , Glutationa/análise , Ventrículos do Coração/diagnóstico por imagem , Peróxido de Hidrogênio/análise , Hipertensão Pulmonar/induzido quimicamente , Hipertensão Pulmonar/diagnóstico por imagem , Masculino , Monocrotalina/toxicidade , Ratos , Ratos Wistar , Tiorredoxina Dissulfeto Redutase/análise , UltrassonografiaRESUMO
Tyrosinase-positive albinism, previously diagnosed as Hermansky-Pudlak Syndrome (HPS), has been examined in four generations from a village of the canton Valais, Switzerland. Homozygotes, obligate heterozygotes and putative heterozygotes in this geneology yielded lower than normal membrane-associated thioredoxin reductase (TR) activities compared with normal family members and controls. All of the homozygotes and 50% of each the obligate and putative heterozygotes showed an increase in bleeding time associated with storage-pool-deficient platelets lacking dense bodies. The TR activity profile and the platelet-dense body deficiency in the Swiss albinos was the same as that in the HPS population from Puerto Rico. However, in albinos from Puerto Rico, there is an accumulation of ceroid/lipofuscin-like pigment in lysosomal structures causing tissue damage, and, upon kidney involvement, this leads to increased urinary dolichol excretion. Approximately half of the Puerto Rican HPS cases had clinical evidence of storage disease with restrictive lung disease, granulomatous colitis, kidney failure and cardiomyopathy. By comparison, the Swiss HPS geneology had a normal life expectancy with no significant evidence for ceroid accumulation or urinary dolichol excretion. An examination of antioxidant enzymes, catalase, TR and glutathione reductase in epidermal suction blisters from Swiss HPS homozygotes showed a similar result for catalase and TR levels to the depigmented epidermis of patients with vitiligo, except that intracellular TR was found to be calcium free in HPS compared with vitiligo. Intracellular glutathione reductase levels were highest in HPS. Both the Swiss and Puerto Rican HPS homozygotes and heterozygotes have giant melanosomes in skin melanocytes.