Clinical study: hypertension
Effect of the angiotensin-converting enzyme inhibitor imidapril on reactive hyperemia in patients with essential hypertension: relationship between treatment periods and resistance artery endothelial function

https://doi.org/10.1016/S0735-1097(00)01177-3Get rights and content
Under an Elsevier user license
open archive

Abstract

OBJECTIVES

The purpose of this study was to evaluate the effects of the angiotensin-converting enzyme (ACE) inhibitor imidapril and the calcium antagonist amlodipine on endothelial function before and after 2, 4, 8, 12, 24 and 48 weeks of treatment.

BACKGROUND

There are limited data on whether and how long endothelial function is improved after initiation of ACE inhibitor treatment and how the grade of endothelial function further progresses after improvement of endothelial dysfunction in patients with essential hypertension.

METHODS

The forearm blood flow (FBF) was measured in 25 patients with essential hypertension and in 25 normotensive subjects by using strain-gauge plethysmography during reactive hyperemia (RH) (280 mm Hg for 5 min) and after sublingual administration of nitroglycerin (NTG, 0.3 mg).

RESULTS

The FBF of patients with essential hypertension during RH was significantly less than that of normotensive subjects. The increase in FBF after sublingual NTG was similar in both groups. Both imidapril (n = 13) and amlodipine (n = 12) significantly reduced systolic blood pressure and diastolic after eight weeks of treatment from the pretreatment values. Forearm vascular resistance was significantly decreased after two weeks of treatment. Imidapril significantly augmented RH after 12 weeks of treatment from the pretreatment values (31.6 ± 5.7 to 38.2 ± 6.0 ml/min per 100 ml tissue, p < 0.05), whereas amlodipine did not alter RH for each treatment period. The ability of imidapril to improve RH was maintained throughout the 48-week treatment period. There was no significant difference in RH at 12, 24 and 48 weeks. The increase in FBF after sublingual administration of NTG was similar in all treatment periods for the two groups. The infusion of NG-monomethyl-L-arginine, a nitric oxide (NO) synthase inhibitor, abolished the enhancement of RH in hypertensive patients treated with imidapril.

CONCLUSIONS

These findings suggest that the ACE inhibitor imidapril augments RH after 12 weeks of treatment in patients with essential hypertension and that this ACE inhibitor-induced augmentation of RH may be due to an increase in NO.

Abbreviations

ACE
angiotensin-converting enzyme
BP
blood pressure
EDHF
endothelium-dependent hyperpolarizing factor
FBF
forearm blood flow
FVR
forearm vascular resistance
L-NMMA
NG-monomethyl-L-arginine
NO
nitric oxide
NTG
nitroglycerin
RH
reactive hyperemia

Cited by (0)

This study was supported in part by a Grant-in-Aid for Scientific Research from the Ministry of Education, Science and Culture of Japan, Tokyo, Japan (Dr. Oshima) and the Japan Heart Foundation Grant for Research on Hypertension and Metabolism, Tokyo, Japan; a Grant for Research Foundation for Community Medicine, Tokyo, Japan; a Grant for Research on Autonomic Nervous System and Hypertension from Kimura Memorial Heart Foundation/Pfizer Pharmaceuticals Inc., Kwume, Japan; and the Foundation for Total Health Promotion, Tokyo, Japan (Dr. Higashi).