Non-specific inhibitors of nitric oxide synthase cause myocardial necrosis in the rat

FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCNPQ – CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOTo study the effect of acute nitric oxide (NO) inhibition on the rat heart both in vitro and in vivo, male Wistar rats received a single bolus injection of saline, N-omega-nitro-L-arginine methyl ester (L-NAME; 0.5, 1.5, 5.0, 15.0 and 45.0 mg/kg) and D-NAME (45.0 mg/kg). 2. Animals were killed 72 h after the bolus injection of L-NAME and the hearts were removed and studied under light microscopy. In other groups of animals, saline, L-NAME and D-NAME were administered as above and the mean arterial blood pressure (MABP/carotid) was recorded, Furthermore, L-NAME was also administered in the drinking water (20 mg/kg per day) for 72 h and animals were then killed and their hearts evaluated as described above, Hearts of control animals were perfused in vitro and coronary flow was measured following saline, L-NAME (45 mu g/heart) and D-NAME (45 mu g/heart). 3. Areas of necrosis were observed in the left ventricle of animals that had received L-NAME at 5.0, 15.0 and 45.0 mg/kg, Also, only doses higher than 1.5 mg/kg caused an important increase in MABP. The frequency and extent of the lesions paralleled the dose of L-NAME administered and no lesions were observed in D-NAME- and saline-treated animals. 4. The oral administration of L-NAME also caused myocardial lesions similar to those described above, but the frequency and extent of these lesions were more discrete compared with those observed following 5.0 mg/kg, i.v., L-NAME. 5. Bolus injection of L-NAME into control rat hearts in vitro resulted in a small and transient fall in coronary flow (17.2 +/- 1.4 and 12.2 +/- 1.2 mL/min before and after L-NAME administration, respectively) within 30 s and this was followed 4.5 min later by a further (11.5 +/- 1.6 mL/min) decrease. The administration of D-NAME to control hearts caused no change in coronary flow. 6. In conclusion, the acute inhibition of NO biosynthesis by L-NAME causes myocardial necrosis, Both high levels of MABP and a small but significant reduction in coronary flow (associated or not) can be responsible for the lesions we found245349352FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCNPQ – CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOFAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCNPQ – CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOsem informaçãosem informaçã