S. Taddei et al., Effect of calcium antagonist or beta blockade treatment on nitric oxide-dependent vasodilation and oxidative stress in essential hypertensive patients, J HYPERTENS, 19(8), 2001, pp. 1379-1386
Citations number
37
Categorie Soggetti
Cardiovascular & Respiratory Systems","Cardiovascular & Hematology Research
Objectives Essential hypertension is associated with impaired endothelium-d
ependent vasodilation caused by oxygen free radical-induced nitric oxide (N
O) breakdown. Since calcium antagonists can improve endothelial function in
hypertensive patients, we tested whether this beneficial effect could be r
elated to restoration of NO availability by antioxidant activity.
Methods In 10 healthy subjects and 20 essential hypertensive patients, we s
tudied forearm blood flow (strain-gauge plethysmography) modifications indu
ced by intrabrachial acetylcholine (from 0.15-15 mug/100 ml per min), brady
kinin (0.005-0.05 mug/100 ml per min), two endothelium-dependent vasodilato
rs, and sodium nitroprusside (1-4 mug/100 ml forearm tissue per min), an en
dothelium independent vasodilator, in the absence and presence of N-G-monom
ethyl-L-arginine (L-NMMA) (100 mug/100 ml forearm tissue per min), an NO sy
nthase inhibitor.
Results In controls, vasodilation to acetylcholine and bradykinin was inhib
ited by L-NMMA. In hypertensive patients, vasodilation to acetylcholine and
bradykinin, but not to sodium nitroprusside, was blunted and resistant to
L-NMMA. Hypertensive patients were randomized to a 12-week treatment with l
acidipine (4-6 mg/daily) or atenolol (50-100 mg/daily) (n = 10 each group).
Lacidipine but not atenolol increased the vasodilation to acetylcholine an
d bradykinin and restored the inhibiting effect Of L-NMMA on endothelium-de
pendent vasodilation, without affecting the response to sodium nitroprussid
e. Moreover, lacidipine reduced circulating markers of oxidative stress inc
luding plasma and low-density lipoprotein (LDL) hydroperoxides, the suscept
ibility of LDL to Cu2+-Induced oxidation and the reactive oxygen species ge
nerated from human umbilical vein endothelial cells after incubation with L
DL derived from plasma of the patients.
Conclusions Lacidipine increases endothelium-dependent vasodilation by rest
oring NO availability, and this effect possibly is related to antioxidant a
ctivity. (C) 2001 Lippincott Williams & Wilkins.