Comparison of Effects of Angiotensin I– Converting Enzyme Inhibition and β-Blockade for 2 Years on Function of Small Arteries From Hypertensive Patients

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Abstract
Abstract The effect of treatment with two different antihypertensive agents on the function of small arteries from 17 patients with essential hypertension randomly assigned to receive either the angiotensin I–converting enzyme inhibitor cilazapril or the β-blocker atenolol was investigated. Subcutaneous small arteries obtained from gluteal fat biopsies were studied on a wire myograph before treatment and at 1 and 2 years of treatment. Blood pressure was mildly elevated in both groups of patients (mean, 150/100 mm Hg) and was well controlled throughout the 2 years of treatment (mean, 130/85 mm Hg). We previously reported, in arteries from patients treated with cilazapril, an improvement at 1 year of treatment of the vasoconstrictor effect of endothelin-1, which had been significantly attenuated in the untreated hypertensive patients compared with normotensive subjects. After 2 years of treatment, this normalization of endothelin-1 response was still present in small arteries of patients treated with the angiotensin I–converting enzyme inhibitor, whereas in patients treated with atenolol, responses were still unchanged after 2 years of treatment. Endothelial function was tested by examining the response of norepinephrine-precontracted arteries to acetylcholine. Untreated hypertensive patients exhibited a slightly but significantly blunted vasorelaxation in response to 10 μmol/L acetylcholine compared with normotensive subjects. After 1 and 2 years of effective antihypertensive treatment, cilazapril-treated patients exhibited responses to acetylcholine that were not different from those of normotensive subjects, whereas atenolol-treated patients still had impaired responses. Thus, together with the correction of the structure of small arteries that we previously reported occurs after 1 or 2 years of treatment with cilazapril, there is persistent normalization of endothelin-1–mediated vasoconstriction and slight improvement of endothelium-dependent vasorelaxation. This suggests that impaired smooth muscle and endothelial function in small arteries of patients with essential hypertension may be corrected by treatment with angiotensin I–converting enzyme inhibitors but not with β-blockers.