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CLINICAL STUDIES

A comparison of angiotensin-converting enzyme inhibitors, calcium antagonists, beta-blockers and diuretic agents on reactive hyperemia in patients with essential hypertension: a multicenter study

Yukihito Higashi, MD, PhD^*, Shota Sasaki, MD^*, Keigo Nakagawa, MD^*, Tomohiro Ueda, MD^*, Atsunori Yoshimizu, MD^*, Satoshi Kurisu, MD^*, Hideo Matsuura, MD, PhD^*, Goro Kajiyama, MD, PhD^* and Tetsuya Oshima, MD, 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 February 8, 1999; revised manuscript received August 24, 1999, accepted October 18, 1999.

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 compare the effect of different antihypertensive agents, calcium antagonists, angiotensin-converting enzyme (ACE) inhibitors, beta-blockers and diuretic agents on endothelial function.

BACKGROUND

Endothelial dysfunction is a component of essential hypertension, and various antihypertensive drugs may be able to restore normal function.

METHODS

Forearm blood flow (FBF) was measured in 296 patients with essential hypertension, including 46 untreated subjects using strain-gauge plethysmography during reactive hyperemia and after sublingual administration of nitroglycerin (NTG). Forty-seven normotensive subjects were similarly evaluated as control subjects.

RESULTS

The FBF during reactive hyperemia in the 296 hypertensive patients was significantly less than that in age-matched normotensive subjects. The increase in FBF after administration of sublingual NTG was similar in both groups. Systolic and diastolic blood pressures and forearm vascular resistance were greater in the untreated group than in the four treated groups and did not differ with respect to the antihypertensive agent used. The maximal FBF response from reactive hyperemia was significantly greater in the ACE inhibitor–treated group than in the group treated with calcium antagonists, beta-blockers, diuretic agents, or nothing (40.5 ± 5.2 vs. 32.9 ± 5.8, 34.0 ± 5.6, 32.1 ± 5.9, and 31.9 ± 5.8 ml/min per 100 ml tissue, p < 0.05, respectively). Reactive hyperemia was similar in the calcium antagonist, beta-blocker, diuretic and untreated groups, and changes in FBF after sublingual NTG administration were similar in all groups. The infusion of N^G-monomethyl-L-arginine, a nitric oxide (NO) synthase inhibitor, abolished the enhancement of reactive hyperemia in hypertensive patients treated with ACE inhibitors.

CONCLUSIONS

These findings suggest that ACE inhibitors augment reactive hyperemia, an index of endothelium-dependent vasorelaxation, in patients with essential hypertension. This augmentation may be due to increases in NO.

Abbreviations and Acronyms   ACE = angiotensin-converting enzyme   ANOVA = analysis of variance   FBF = forearm blood flow   HDL = high density lipoprotein   L-NMMA = NG-monomethyl-L-arginine   NO = nitric oxide   NTG = nitroglycerin

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