IMPAIRMENT OF FOREARM VASODILATATION TO ACETYLCHOLINE IN HYPERCHOLESTEROLEMIA IS REVERSED BY ASPIRIN

Objective: Impaired cholinergic vasodilatation in the forearm in hyper tension and hypercholesterolemia has been attributed to impaired nitri c oxide bioavailability. However, inhibition of cyclooxygenase reverse s the impaired cholinergic dilatation in hypertensive animals and pati ents. The aim of this study was to examine the effect of aspirin on ch olinergic vasodilatation in hypercholesterolemic patients. Methods: We examined responses to brachial artery infusion of acetylcholine and t he endothelium-independent vasodilator sodium nitroprusside in the pre sence or absence of aspirin in 10 hypercholesterolemic patients (7 men /3 women; aged 38-63 yr; systolic blood pressure 133 +/- 5 mmHg; diast olic blood pressure SO +/- 3) compared with 10 matched controls (7 men /3 women: aged 38-63 yr; systolic blood pressure 126 +/- 2; diastolic blood pressure 77 +/- 2). Results: In hypercholesterolemic patients, f orearm vasodilatation was impaired in response to acetylcholine (112 /- 20 vs. 346 +/- 30% increase in blood now in controls, at the highes t dose [15 mu g min(-1)]; P < 0.0001) but not in response to sodium ni troprusside. With the addition of aspirin, baseline forearm blood flew was unaltered. However, forearm vasodilatation to acetylcholine was p artially restored in hypercholesterolemics (from 112 +/- 20 to 193 +/- 30%; P < 0.001) though not affected in controls. Vasodilator response s to sodium nitruprusside were unaffected by aspirin in either group. Conclusions: In hypercholesterolemia, an altered balance between vasoc onstrictor and dilator prostanoids. favouring constrictors, may contri bute to endothelial dysfunction either directly or through an effect o n nitric oxide synthesis. Restoration of this imbalance may be a compo nent of the therapeutic benefit of aspirin in cardiovascular disease. (C) 1998 Elsevier Science B.V. All rights reserved.