Inibição da sintese de oxido nitrico em ratos wistar : efeitos sobre a morfologia e a função cardiacas

AUTOR(ES)
DATA DE PUBLICAÇÃO

1995

RESUMO

This thesis examines the effects of acute and chronic inhibition of nitric oxide (NO) biosynthesis on cardiac function and morphology in Wistar rats. The contribution of angiotensin 11 to the cardiac changes observed following chronic NO inhibition was evaluated by treating the animais with enalapril, an angiotension converting enzyme inhibitor. Chronic inhibition of NO biosvnthesis: The five groups of rats employed in this first part of the study included a control group (C), a two kidney-one clip (2K-1 C) group, an L-NAME (N°O-nitro-L-arginine methyl ester, 65 mg/kg/day, orally) group, a 2K-1 C+L-NAME (same dose as above) group, and a D-NAME (NÚL nitro-D-arginine methyl ester, 65 mg/kg/day, orally) group. The body weight (8W) and caudal arteriàl blood pressure (CAP) of each rat were measured weekly. In selected animais from each of these groups, the cardiac mass was also determined two, four and eight weeks after the start of the study. At the eighth week, the control and L-NAME-treatedanimals were sacrificed and their hearts isolated and perfused by the method of Llangendorff. For each heart, the left ventricular developed pressure (LVDP) and coronary flow (CF) were determined. The hearts of rats from each group were also exami.ned histologically by light microscopy. The oral administration of L-NAME produced hypertension which was maximal after five weeks. Only after the sixth week was the arterial tail cuff pressure in the 2K-1C rats significantly greater than in the animais receiving LNAME. 80th the LVDP aríd CF of L-NAME-treated nat hearts were significantly less than those of the control animais. The lower LVDP suggests a decreased contractile capacity in the former group. There were no significant differences in the left ventricular end-diastolic pressure (LVEDP) or in the heart rate between the L-NAME-treated and control groups. The relative body weight (BWr) and the relative left ventricular weight (LVWr) were greater in the 2K-1C and 2K-1C+L-NAME groups than in the control and L-NAME alone groups after two and four weeks. By the eighth week, the BWr and LVWr of the L-NAME group were higher than in the control animais but similar to those of the two 2K-1 C groups. Histologically, none of the hearts in the control and D-NAME groups was classified as having necrosis and in the 2K-1 C group the incidence of cardiac alterations was low. In contrast, the rats treated with L-NAME developed myocardial changes the severity of which increased with the length of treatment. Although arterial pressure was elevated to a similar extent in the three groups of hypertensive animais, those receiving L-NAME showed the most severe and extensive lesions. This observation indicates that an elevated arterial pressure alone cannot explain the changes encountered. Areas of myocardial necrosis appeared early in the L-NAME group (by the second week) , at which time left ventricular hypertrophy (L VH) had not yet developed. These findings, together with the decreased CF, suggest ischemia as the cause for the changes occurring in L-NAME-treated animais. Based on the foregoing results, it is concluded that the chronic inhibition of NO biosynthesis leads to myocardial ischemia with myofibrillar necrosis and interstitial fibrosis. These alterations may represent the morphological correlate of the functional deficit in myocardial contractility described above. The principal factor involved in initiating this ischemia is likely to be the decrease in lhe oxygen supply to myocardial tissue as a consequence of a reduced CF. This suggestion is supported by lhe observation that the ischemic lesions preceded J the onset of L VH. Effect of enalapril (ENAL) on the cardiovascular alterations induced bv the chronic inhibition of NO biosvnthesis: The animais used in this part of the study were divided into four groups as follows: control, L-NAME-treated (same dose as used above), L-NAME+ENAL-treated (25 mg of enalapril maleate/kg/day, orally), and ENAL-treated (same dose as in the foregoing group). The changes in BW and CAP were monitored over a period of eight weeks after which time the BWr and L VWr were determined. In addition, the functional activity and histology of the hearts were examined as described above. Enalapril abolished the L-NAME-induced arterial hypertension after the second week and prevented both the development of left ventricular hypertrophy and the loss of myocardial contractility. This drug did not, however, interfere with either the decrease in CF or the appearance of ischemic myocardial lesions. These results suggest that two distinct pathophysiological mechanisms are involved in the L-NAME-induced effects, namely, (1) an increased activity of the renin-angiotensin system associated with the elevated arterial blood pressure and LVH, and (2) the appearance of structural and or functional coronary vascular alterations which lead to the ischemic lesions observed

ASSUNTO(S)

hipertrofia endotelio isquemia hipertensão

ACESSO AO ARTIGO

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