enalapril and Vascular-Diseases

A protective role against atherosclerosis can be attributed to angiotensin converting enzyme inhibitors (ACE-I), since they have been shown to reduce mortality in patients at cardiovascular risk. Since plasma levels of adhesion molecules are considered surrogate markers of endothelial cell activation and atherogenesis, we compared the levels of adhesion molecules after treatment with the ACE-I enalapril or the direct angiotensin- receptor antagonist losartan or placebo. In a randomized, controlled trial, 21 hypercholesterolemic volunteers received 50 mg/d losartan or 20 mg/d enalapril or placebo for twelve weeks. Plasma levels of circulating intercellular adhesion molecule-1 (cICAM-1), vascular adhesion molecule-1 (cVCAM-1), and E-selectin (cE-SEL) were measured by ELISA. Surface expression of ICAM-1 on circulating leukocytes was determined by flow cytometry. Enalapril and losartan but not placebo induced a small but stable decrease of cICAM-1 and cVCAM-1, while cE-SEL and leukocyte expression of ICAM-1 remained unchanged. The lowering of plasma adhesion molecules may indicate an antiatherogenic effect of angiotensin II blockade in hypercholesterolemia. While such preventive effect will have to be proven in clinical trials, our results do not support a preference for either enalapril or losartan with regard to their possible vasoprotective role.

Topics: Angiotensin Receptor Antagonists; Blood Pressure; Cholesterol; Double-Blind Method; E-Selectin; Enalapril; Enzyme-Linked Immunosorbent Assay; Female; Flow Cytometry; Humans; Hypercholesterolemia; Inflammation; Intercellular Adhesion Molecule-1; Leukocytes; Losartan; Male; Middle Aged; Pilot Projects; Receptors, Angiotensin; Vascular Cell Adhesion Molecule-1; Vascular Diseases

Topics: Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Animals; Coronary Disease; Enalapril; Heart Transplantation; Losartan; Models, Animal; Postoperative Complications; Rats; Rats, Inbred F344; Rats, Inbred Lew; Receptor, Angiotensin, Type 1; Vascular Diseases

Hyperuricemia is associated with hypertension and vascular disease, but whether this represents a causal relationship or an epiphenomenon remains unknown. We recently reported a model of mild hyperuricemia in rats that results in increased blood pressure and mild renal fibrosis. In this study, we examined the effect of hyperuricemia on the renal vasculature. Rats fed 2% oxonic acid and a low-salt diet for 7 wk developed mild hyperuricemia (1.8 vs. 1.4 mg/dl, P < 0.05), hypertension [147 vs. 127 mmHg systolic blood pressure (SBP), P < 0.05], and afferent arteriolar thickening, with a 35% increase in medial area (P < 0.05). Allopurinol or benziodarone prevented the hyperuricemia, hypertension, and arteriolopathy. Hydrochlorothiazide treatment did not prevent the hyperuricemia or arteriolopathy despite controlling blood pressure. In contrast, the arteriolopathy and hypertension were prevented by both enalapril and losartan. Uric acid also directly stimulated vascular smooth muscle cell proliferation in vitro, and this was partially inhibited by losartan. Thus hyperuricemia induces a renal arteriolopathy in rats that is blood pressure independent and involves the renin-angiotensin system.

Topics: Administration, Oral; Allopurinol; Angiotensin II; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Animals; Arterioles; Benzofurans; Blood Pressure; Diuretics; Enalapril; Hydrochlorothiazide; Hypertension; Kidney; Losartan; Male; Muscle, Smooth, Vascular; Oxonic Acid; Rats; Rats, Sprague-Dawley; Sodium Chloride Symporter Inhibitors; Sodium Chloride, Dietary; Uric Acid; Uricosuric Agents; Vascular Diseases