Or. Coelho et al., Pravastatin reduces myocardial lesions induced by acute inhibition of nitric oxide biosynthesis in normocholesterolemic rats, INT J CARD, 79(2-3), 2001, pp. 215-221
Citations number
32
Categorie Soggetti
Cardiovascular & Respiratory Systems","Cardiovascular & Hematology Research
Pravastatin is useful in restoring endothelium-dependent relaxation in hype
rcholesterolemic animals. A single intravenous bolus injection of N-omega-n
itro-L-arginine methyl ester (L-NAME), a non-specific inhibitor of NO synth
ase, causes myocardial necrosis and reduces coronary flow in rats. Since ra
ts do not develop hypercholesterolemia and atherosclerosis, we have tested
the hypothesis that pravastatin protects the heart from myocardial lesions
induced by L-NAME in the absence of alterations in cholesterol levels and p
laque formation. Male Wistar rats fed standard chow were divided into four
groups: CONTROL (n=14) - rats that received tap water alone for 18 days; L-
NAME (n=14) - rats that received L-NAME (15 mg/kg, i.v.) on the 14th day of
the study; PRAVASTATIN (n=11) - rats that received pravastatin (6 mg/kg/da
y) in their drinking water for 18 days; PRAVASTATIN+L-NAME (n=12) - rats th
at received pravastatin (6 mg/kg/day) and L-NAME (15 mg/kg, i.v.) as indica
ted in the preceding groups. At the end of 18 days, the rats were sacrifice
d and the hearts removed for stereological analysis by light microscopy. Pl
asma nitrate/nitrite and thromboxane B-2 concentrations were determined imm
ediately before and after L-NAME administration. Pravastatin prevented the
ischemic lesions induced by the acute inhibition of NO biosynthesis (the ar
ea of myocardial lesions in the L-NAME group was greater than in the Pravas
tatin+L-NAME group: 101.6 mum(2) vs. 1.2 mum(2), respectively; P <0.0001) a
nd markedly increased the plasma nitrate/nitrate concentrations, even befor
e L-NAME administration. There were no significant changes in the plasma th
romboxane B-2 concentrations. (C) 2001 Elsevier Science Ireland Ltd. All ri
ghts reserved.