VASCULAR DYSFUNCTION IN MONKEYS WITH DIET-INDUCED HYPERHOMOCYST(E)INEMIA

Elevated plasma homocyst(e)ine may predispose to complications of vasc ular disease, Homocysteine alters vasomotor regulatory and anticoagula nt properties of cultured vascular endothelial cells, but little is kn own about effects of hyperhomocyst(e)inemia on vascular function in vi vo. We tested the hypothesis that diet-induced moderate hyperhomocyst( e)inemia is associated with vascular dysfunction in cynomolgus monkeys . Plasma homocyst(e)ine increased from 4.0+/-0.2 mu M when monkeys wer e fed normal diet to 10.6+/-2.6 mu M when they were fed modified diet (mean+/-SE; P = 0.02). Vasomotor responses were assessed in vivo by qu antitative angiography and Doppler measurement of blood flow velocity. In response to activation of platelets by intraarterial infusion of c ollagen, blood flow to the leg decreased by 42+/-9% in monkeys fed mod ified diet, compared with 14+/-11% in monkeys fed normal diet (P = 0.0 08). Responses of resistance vessels to the endothelium-dependent vaso dilators acetylholine and ADP were markedly impaired in hyperhomocyst( e)inemic monkeys, which suggests that increased vasoconstriction in re sponse to collagen may be caused bq decreased vasodilator responsivene ss to platelet-generated ADP. Relaxation to acetylcholine and, to a le sser extent, nitroprusside, was impaired ex vivo in carotid arteries f rom monkeys fed modified diet. Thrombomodulin anticoagulant activity i n aorta decreased by 34+/-15% in hyperhomocyst(e)inemic monkeys (P = 0 .03). We conclude that diet-induced moderate hyperhomocyst(e)inemia is associated with altered vascular function.