AIM: To study the effect of the angiotensin-converting enzyme (ACE) in
hibitors perindopril (Per) and enalaprilat (Ena) on the reactivity of
the endothelium in normal rats. METHODS: Male rats were treated intrag
astrically with Per (2 mg . kg(-1). d(-1)) or placebo (n = 18) for 6 w
k. Aorta was isolated for experiment. isolated aortic rings with and w
ithout endothelium were incubated with Ena (0.1 mu mol . L(-1)) for 30
min. Responses to acetylcholine, serotonin, phenylephrine, sodium nit
roprusside (SN), and nitroglycerin (Nit) were observed. RESULTS: Endot
helium-dependent relaxation to acetylcholine was augmented in aortic r
ings from rats treated with Per in comparison with control. The lc, va
lue (95 % confidence limits) decreased from 3.8 (0.56 - 26.1) mu mol .
L(-1) (control group) to 0.98 (0.28 - 3.41) mu mol . L(-1) (Per-treat
ed group). The maximal relaxation was augmented from 62 +/- 9 % to 78
+/- 10 % (P < 0.01). However, the responses to the endothelium-indepen
dent vasodilators, SN and Nit, were similar. Serotonin- and phenylephr
ine-induced contractions were decreased, which were influenced by basa
l release of endothelium-derived relaxing factor (EDRF). EC(50) value
was 6.1 (2.6 - 14.4) nmol . L(-1) vs 8.3 (3.6 - 18.8) nmol . L(-1) in
comparison with control group and Per-treated group. The maximal contr
action was decreased from 2.42 +/- 0.29 g (control group) to 1.96 +/-
0.25 g (treated group) (P < 0.01). Similar results were found in incub
ation with Ena. CONCLUSION: Ena and Per enhanced the basic release of
EDRF from vascular endothelium.