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


METHODS
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.


METHODS
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.


RESULTS
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).


CONCLUSIONS
Isradipine improves acetylcholine-mediated vasodilation in hypercholesterolemic patients independent of changes in lipids or blood pressure.
Bracht
C
C
Department of Medicine, University Hospital Zürich, Switzerland.
Yan
X W
XW
Brunner-LaRocca
H P
HP
Sütsch
G
G
Amann
F W
FW
Kiowski
W
W
D000368:Aged; D001794:Blood Pressure / Q000187:drug effects; D002784:Cholesterol / Q000097:blood; D003327:Coronary Disease / Q000150:complications* / Q000188:drug therapy / Q000503:physiopathology*; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000502:physiology*; D005542:Forearm / Q000098:blood supply; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood / Q000150:complications*; D017275:Isradipine / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D012016:Reference Values; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology*; D014665:Vasodilator Agents / Q000627:therapeutic use*
D014665:Vasodilator Agents; D002784:Cholesterol; D017275:Isradipine