Correction of Remodeling and Function of Small Arteries in Human Hypertension by Cilazapril, an Angiotensin I-Converting Enzyme Inhibitor

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Abstract
Angiotensin II may contribute to the altered structure and function of small arteries. We proposed that angiotensin I-converting enzyme (ACE) inhibitor treatment could induce a regression of vascular remodeling. A double-blind trial was performed comparing effects of the ACE inhibitor cilazapril with the beta-blocker atenolol on small arteries obtained from biopsy specimens of subcutaneous gluteal fat. Nine patients with essential hypertension were randomized to cilazapril and eight to atenolol. Blood pressure was below 140/95 mm Hg under treatment for the duration of the study in all patients. Media-to-lumen ratio of small arteries of the patients, which before treatment was significantly higher than in normotensive subjects, was corrected after 1 year of treatment in the cilazapril group. There was no change in the increased media-to-lumen ratio of small arteries in the atenolol group, even after 2 years of treatment. Attenuated constrictor responses to endothelin-1 returned to normal only in the patients treated with cilazapril. Endothelium-dependent relaxation responses to acetylcholine were slightly depressed in hypertensive patients and improved in the cilazapril-treated group, but remained blunted in the arteries of the atenolol-treated patients. Treatment with cilazapril corrects small artery remodeling and endothelium-related functional abnormalities of gluteal subcutaneous small arteries in hypertensive patients. It remains to be demonstrated whether these apparently beneficial effects translate into reduced morbidity and mortality in hypertension.