Efeitos da associação do treinamento físico aeróbio e baixa dose de L-NAME sobre cardiomiócitos isolados

Abstract

Introduction: Nitric oxide (NO) is a soluble gas and its messenger capacity is extremely important, activating or inhibiting several target molecules involved in various physiological processes. The short and medium-term inhibition of NO production leads to a series of deleterious effects on the cardiovascular system. High doses (20-100 mg/kg) of NG-nitro-Larginine methyl ester (L-NAME) promote arterial hypertension, increased myocardial collagen fraction with consequent elevation of fibrosis and necrosis, as well as functional impairment. However, low doses of L-NAME (0.5-10 mg/kg) appears to increase the activity of nitric oxide synthases (NOS) in the aorta and left ventricle (LV), reversing the increase in blood pressure (BP). These results suggest that low-dose of L-NAME can activate NO synthesis by negative feedback and, consequently, promote benefits to the cardiovascular system. Physical exercise is also associated to several cardioprotective effects, besides causing increased bioavailability of NO and expression and activity of endothelial nitric oxide synthase (eNOS). Objective: To evaluate the effects of association of aerobic exercise training and low-dose of L-NAME on the process of cardiac remodeling, contractile parameters and calcium (Ca2+) handling in isolated cardiomyocytes. Methods: Wistar rats (n = 56) were randomly assigned into four groups: control (C), L-NAME (L), exercise (Ex), and exercise + L-NAME (ExL). The exercised groups performed aerobic physical training with progressive intensity increase (50 to 80% of maximum running speed) for 12 weeks. LNAME was given daily by orogastric gavage at 1.5 mg/kg/day. Body adiposity, pressure profile, cardiac morphology, myocyte cross sectional area (CSA), myocardial collagen, cardiac contractility parameters and intracellular Ca2+ handling were analyzed. Data were expressed as mean ± standard error of the mean. The significance level considered was 5%. Results: Association of chronic aerobic exercise and low-dose of L-NAME promoted in significantly increased systolic BP (at week 8) and LV end-diastolic-pressure (at week 12), as well as increased heart/tibia ratio and interstitial collagen fraction, but with reduction of CSA. In addition, the shortening and times to 50% shortening and relaxation were lower in ExL in relation to L and Ex. The Ca2+ transient amplitude and the time to 50% peak Ca2+ were higher in the ExL, however, this association brought lower time to 50% Ca2+ decay. Conclusion: Association of chronic aerobic exercise and low-dose of L-NAME does not promote benefits to the cardiovascular system, since it causes cardiac remodeling with increase in the synthesis of collagen and LV end-diastolic-pressure, as well as contractile dysfunction evidenced by reduction of the percentage of shortening. The findings also indicate that this association promotes an increase in sensitivity to Ca2+intracellular.