Endothelium-dependent effect of perindopril and enalaprilat in rat thoracic aorta.
OBJECTIVE
To study the effect of the angiotensin-converting enzyme (ACE) inhibitors perindopril (Per) and enalaprilat (Ena) on the reactivity of the endothelium in normal rats.


METHODS
Male rats were treated intragastrically with Per (2 mg.kg-1.d-1) or placebo (n = 18) for 6 wk. Aorta was isolated for experiment. Another set of isolated aortic rings with and without endothelium were incubated with Ena (0.1 mumol.L-1) for 30 min. Responses to acetylcholine, serotonin, phenylephrine, sodium nitroprusside (SN), and nitroglycerin (Nit) were observed.


RESULTS
Endothelium-dependent relaxation to acetylcholine was augmented in aortic rings from rats treated with Per in comparison with control. The IC50 value (95% confidence limits) decreased from 3.8 (0.56-26.1) mumol.L-1 (control group) to 0.98 (0.28-3.41) mumol.L-1 (Per-treated group). The maximal relaxation was augmented from 62 +/- 9% to 78 +/- 10% (P < 0.01). However, the responses to the endothelium-independent vasodilators, SN and Nit, were similar. Serotonin- and phenylephrine-induced contractions were decreased, which were influenced by basal release of endothelium-derived relaxing factor (EDRF). EC50 values 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 contraction 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 incubation with Ena.


CONCLUSIONS
Ena and Per enhanced the basic release of EDRF from vascular endothelium.
Fang
Z Y
ZY
Shanxi Cardiovascular Institute, Taiyuan, China.
Li
Y F
YF
Zhang
L L
LL
Liu
D J
DJ
Li
Y Q
YQ
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D015773:Enalaprilat / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009569:Nitric Oxide / Q000096:biosynthesis; D020913:Perindopril; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar
D000806:Angiotensin-Converting Enzyme Inhibitors; D007211:Indoles; D009569:Nitric Oxide; D015773:Enalaprilat; D020913:Perindopril