R. Maeso et al., Effects of antihypertensive therapy on factors mediating endothelium-dependent relaxation in rats treated chronically with L-NAME, J HYPERTENS, 17(2), 1999, pp. 221-227
Citations number
25
Categorie Soggetti
Cardiovascular & Respiratory Systems","Cardiovascular & Hematology Research
Objectives To evaluate the relative participation of endothelium-derived fa
ctors mediating relaxation in response to acetylcholine in isolated mesente
ric vascular beds from rats treated chronically with NG-nitro-L-arginine me
thylester (L-NAME); and to compare the consequences of prolonged treatment
with either an angiotensin converting enzyme inhibitor or a calcium channel
blocker on the components of acetylcholine-induced relaxation in this vasc
ular preparation.
Materials and methods Male Sprague-Dawley rats were treated for 8 weeks wit
h L-NAME (40 mg/kg per day), quinapril (10 mg/kg per day), diltiazem (100 m
g/kg per day), L-NAME + quinapril and L-NAME + diltiazem. Systolic blood pr
essure was estimated by a tail-cuff plethysmograph. Relaxing responses to a
cetylcholine (10(-12) to 10(-8) mol) in mesenteric vascular beds precontrac
ted with phenylephrine (10(-5) mol/l) were studied in the presence and abse
nce of L-NAME (10(-5) mol/l), L-NAME + indomethacin (10(-5) mol/l) or L-NAM
E + indomethacin + potassium chloride (6 x 10(-5) mol/l). The area under th
e dose-response curve was used to calculate the approximate participation o
f nitric oxide, prostaglandins or endothelium-derived hyperpolarizing facto
r in the acetylcholine-induced relaxation.
Results Chronic administration of L-NAME increased blood pressure levels an
d vascular responsiveness to phenylephrine. Treatments with either quinapri
l or diltiazem reduced blood pressure levels and attenuated the increased r
esponse to phenylephrine. Relaxing responses to acetylcholine were similar
in all groups, independently of the treatment received. The calculated part
icipation of endothelium-derived hyperpolarizing factor in the acetylcholin
e-induced relaxation was higher than that of nitric oxide and prostaglandin
s in all groups, but was higher in L-NAME-treated than in untreated rats. I
n contrast, the participation of both nitric oxide and prostaglandins was h
igher in control than in L-NAME-treated rats. Quinapril increased the parti
cipation of prostaglandins in L-NAME-treated rats. Diltiazem increased the
participation of nitric oxide in L-NAME-treated rats.
Conclusions The administration of L-NAME in Sprague-Dawley rats increased t
he production of endothelium-derived hyperpolarizing factor as a compensato
ry mechanism to maintain acetylcholine-induced relaxation. Antihypertensive
therapy with either quinapril or diltiazem produced a selective redistribu
tion of the endothelial factors mediating acetylcholine-induced relaxation.
(C) Lippincott Williams & Wilkins.