Isradipine improves endothelium-dependent vasodilation in normotensive coronary artery disease patients with hypercholesterolemia

• Published in: Journal of hypertension Vol. 19; no. 5; p. 899
• Main Authors: Bracht, C, Yan, X W, Brunner-LaRocca, H P, Sütsch, G, Amann, F W, Kiowski, W
• Format: Journal Article
• Language: English
• Published: England 01.05.2001
• Subjects: Aged; Blood Pressure - drug effects; Cholesterol - blood; Coronary Disease - complications; Coronary Disease - drug therapy; Coronary Disease - physiopathology; Double-Blind Method; Endothelium, Vascular - physiology; Forearm - blood supply; Humans; Hypercholesterolemia - blood; Hypercholesterolemia - complications; Isradipine - therapeutic use; Male; Middle Aged; Reference Values; Vasodilation - drug effects; Vasodilation - physiology; Vasodilator Agents - therapeutic use
• ISSN: 0263-6352
• DOI: 10.1097/00004872-200105000-00010

The dihydropyridine calcium antagonist isradipine has anti-atherosclerotic effects in animals and improves endothelium-mediated nitric oxide (NO)-dependent vasodilation in vitro. As improved endothelial function may be beneficial we investigated its effects in patients with a high likelihood of endothelial dysfunction. Thirty patients (two female, age 55.4 +/- 10.5 years) with known coronary artery disease and elevated (> 6 mmol/l) total cholesterol (cholesterol: mean 6.7 +/- 0.78 mmol/l) or a cholesterol/high density lipoproteins (HDL) ratio of > 5 not on lipid lowering therapy, participated in the study. Endothelial vasodilator function was assessed before and after double-blind, randomized administration of isradipine 5 mg/day or placebo for 3 months. Endothelial function was assessed as forearm blood flow (FBF, venous occlusion plethysmography) responses to graded brachial artery infusions of acetylcholine (Ach), to the NO-synthase blocker NG-monomethyl-L-arginine (L-NMMA) and to the endothelium-independent vasodilator sodium nitroprusside (SNP). Blood pressure was measured either directly from the brachial arterial or by sphygmomanometer during clinic visits. Blood pressure was unchanged in both groups after 3 months (isradipine: 88.8 versus 92.1 mmHg; placebo: 81.0 versus 82.5 mmHg; NS) but cholesterol levels decreased similarly in both groups (isradipine: 6.7 versus 6.1 mmol/l, NS; placebo: 6.6 versus 5.9 mmol/l, P< 0.05). The vasodilator response to SNP and the decrease in FBF in response to blockade of NO synthesis by L-NMMA were unchanged in both groups. However, isradipine, but not placebo, enhanced the NO-dependent vasodilator response to Ach (P < 0.05). Isradipine improves acetylcholine-mediated vasodilation in hypercholesterolemic patients independent of changes in lipids or blood pressure.