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

Objective The dihydropyridine calcium antagonist isradipine has anti-athero sclerotic 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 likelihoo d of endothelial dysfunction. Design Thirty patients (two female, age 55.4 +/- 10.5 years) with known cor onary artery disease and elevated (> 6 mmol/l) total cholesterol (cholester ol: mean 6.7 +/- 0.78 mmol/l) or a cholesterol/high density lipoproteins (H DL) 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. Methods Endothelial function was assessed as forearm blood flow (FBF, venou s occlusion plethysmography) responses to graded brachial artery infusions of acetylcholine (Ach), to the NO-synthase blocker N-G-monomethyl-L-arginin e (L-NMMA) and to the endothelium-independent vasodilator sodium nitropruss ide (SNP). Blood pressure was measured either directly from the brachial ar terial or by sphygmomanometer during clinic visits, Results Blood pressure was unchanged in both groups after 3 months (isradip ine: 88.8 versus 92.1 mmHg; placebo: 81.0 versus 82.5 mmHg; NS) but cholest erol 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 resp onse 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 plac ebo, enhanced the NO-dependent vasodilator response to Ach (P < 0.05). Conclusion Isradipine improves acetylcholine-mediated vasodilation in hyper cholesterolemic patients independent of changes in lipids or blood pressure , J Hypertens 19:899-905 (C) 2001 Lippincott Williams & Wilkins.