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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

Yukihito Higashi, MD, PhD^*, Shota Sasaki, MD^*, Keigo Nakagawa, MD^*, Hideo Matsuura, MD, PhD^*, Goro Kajiyama, MD, PhD^* and Tetsuya Oshima, PhD

^* First Department of Internal Medicine, Hiroshima University School of Medicine, Hiroshima, Japan
Department of Clinical Laboratory Medicine, Hiroshima University School of Medicine, Hiroshima, Japan

Manuscript received June 7, 2000; revised manuscript received September 22, 2000, accepted November 3, 2000.

Reprint requests and correspondence: Dr. Yukihito Higashi, Hiroshima University School of Medicine, First Department of Internal Medicine, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan
yhigashi{at}mcai.med.hiroshima-u.ac.jp

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 N^G-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 and Acronyms   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

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