Par. Jorge et al., RAPID REVERSAL OF ENDOTHELIAL DYSFUNCTION IN HYPERCHOLESTEROLEMIC RABBITS TREATED WITH SIMVASTATIN AND PRAVASTATIN, Clinical and experimental pharmacology and physiology, 24(12), 1997, pp. 948-953
1. The main objective of the present study was to verify the speed wit
h which two 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors
, simvastatin and pravastatin, could revert endothelial cell dysfuncti
on in hypercholesterolaemic rabbits. An attempt was also made to corre
late the plasma cholesterol level and the tissue cholesterol and malon
dialdehyde (MDA) contents of the aortae with the endothelium-dependent
relaxation on the assumption that any endothelial dysfunction could b
e rapidly and partially reversed, even in the presence of relatively h
igh serum cholesterol levels. 2. Ninety-one male New Zealand white rab
bits were randomly assigned to hypercholesterolaemic (control), simvas
tatin or pravastatin groups. All rabbits were fed a diet supplemented
with cholesterol (0.5%) and coconut oil (2%) for 8 weeks. Simvastatin
(10 and 20 mg/day) and pravastatin (15 and 30 mg/day) were administere
d 6, 4, and 2 days before the end of the experiment. At the end of the
8th week, animals were killed and the aortae were removed for histolo
gical examination as well as for the measurement of cholesterol and MD
A contents and for endothelium-dependent relaxation studies. 3. The re
sults showed that significant improvement in endothelium-dependent rel
axation was obtained only with pravastatin and only with 4 or 6 days o
f administration. In these cases, the cholesterol and MDA contents of
the vessel wall were reduced, although no significant changes were obs
erved in plasma total cholesterol. Higher doses of the drugs did not a
lter these results. 4. We conclude that pravastatin enhances endotheli
um-dependent relaxation when administered to cholesterol-fed rabbits,
probably via an anti-oxidant action. This effect, which was observed t
o start on the 4th day of drug administration, may represent a new the
rapeutic approach for the treatment of acute coronary syndromes in hyp
ercholesterolaemic patients.