EFFECT OF INCREASED AVAILABILITY OF ENDOTHELIUM-DERIVED NITRIC-OXIDE PRECURSOR ON ENDOTHELIUM-DEPENDENT VASCULAR RELAXATION IN NORMAL SUBJECTS AND IN PATIENTS WITH ESSENTIAL-HYPERTENSION
Ja. Panza et al., EFFECT OF INCREASED AVAILABILITY OF ENDOTHELIUM-DERIVED NITRIC-OXIDE PRECURSOR ON ENDOTHELIUM-DEPENDENT VASCULAR RELAXATION IN NORMAL SUBJECTS AND IN PATIENTS WITH ESSENTIAL-HYPERTENSION, Circulation, 87(5), 1993, pp. 1475-1481
Background. Patients with essential hypertension have a deficit in the
endothelium-derived nitric oxide system that results in impaired endo
thelium-dependent vascular relaxation. The objective of this study was
to determine whether this abnormality is caused by a deficiency of su
bstrate for nitric oxide synthesis. Methods and Results. The vascular
responses to acetylcholine (an endothelium-dependent vasodilator infus
ed at 7.5, 15, and 30 mug/min) and sodium nitroprusside (a direct smoo
th muscle dilator infused at 0.8, 1.6, and 3.2 mug/min) were studied d
uring combined administration of dextrose 5% or L-arginine (substrate
for nitric oxide synthesis infused at 40 mumol/min) in 12 normal contr
ol subjects (seven men and five women; age, 49.3+/-7 years) and 14 hyp
ertensive patients (nine men and five women; age, 48.4+/-7 years). In
addition, the effect Of D-arginine (stereoisomer of arginine that is n
ot a precursor of nitric oxide) on the vascular responses to acetylcho
line was studied in eight normal control subjects and seven hypertensi
ve patients. Drugs were infused into the brachial artery, and the resp
onse of the forearm vasculature was measured by strain gauge plethysmo
graphy. The vasodilator response to acetylcholine was significantly bl
unted in hypertensive patients compared with normal control subjects (
maximum flow, 8.9+/-5 versus 15.7+/-6 mL . min-1 . 100 mL-1, respectiv
ely; p < 0.007); however, no difference was observed in the response t
o sodium nitroprusside (11.4+/-6 and 11.7+/-mL . min-1 . 100 mL-1, res
pectively). L-Arginine did not significantly change basal blood flow o
r vascular resistance in either group. In normal control subjects, the
infusion Of L-arginine significantly augmented the vasodilator respon
se to acetylcholine (maximum How, 15.7+/-6 versus 21.4+/-8 mL . min-1
. 100 ml-1 before and after L-arginine, respectively p < 0.001). In co
ntrast, in hypertensive patients, the infusion of L-arginine did not a
lter the response to acetylcholine (maximum flow, 8.9+/-5 and 8.4+/-4
mL . min-1 . 100 mL-1 before and after L-arginine, respectively). The
administration of L-arginine did not modify the response to sodium nit
roprusside in either group. Similarly, the infusion of D-arginine did
not alter the response to acetylcholine in either group. Conclusions.
In normal humans, availability of substrate for production of nitric o
xide is a rate-limiting step for endothelium-dependent vascular relaxa
tion. In contrast, increased availability of nitric oxide precursor do
es not modify endothelium-mediated vasodilation in hypertensive patien
ts. These findings provide further evidence of a defect in the endothe
lium-derived nitric oxide system in hypertension and indicate that thi
s abnormality is not related to decreased availability of substrate fo
r nitric oxide production.