IMPAIRED VASODILATOR FUNCTION OF NITRIC-OXIDE ASSOCIATED WITH DEVELOPING NEO-INTIMA IN CONSCIOUS RABBITS

The aim of this study was to use periarterial manipulation to produce an atheroma-like neo-intima in rabbits and study resting blood flow an d vascular responsiveness in vivo. One common carotid artery was enclo sed in a silastic collar to induce a neo-intima similar to that of hum an early atherosclerosis, and carotid blood flow was measured periodic ally over 8 days in 8 conscious rabbits. The vasodilator responses to intravenous infusions of the endothelium-dependent vasodilator, acetyl choline, and glyceryl trinitrate were measured in each artery at 2 and 7 days after surgical placement of the collar, and again following in fusion of the nitric oxide synthase inhibitor, N-nitro-L-arginine (NOL A, 15 mg/kg). Histological examination of the arterial segments at com pletion of the study revealed significant intimal thickening of the re gions of artery enclosed in the collar. Resting blood flow was lower i n the collared vascular bed as compared with the control, from as earl y as 2 days after surgery. Acetylcholine- and glyceryl trinitrate-indu ced decreases in carotid resistance, however, were no different betwee n the arteries after 2 days. At 7 days after surgery, the vasodilator response to acetylcholine was significantly impaired in the collared v ascular bed when compared with the control, while the glyceryl trinitr ate-induced vasodilatation was similar in the two beds. Following NOLA infusion, mean arterial pressure was significantly increased and bloo d flow through both arteries was reduced. After NOLA, acetylcholine-in duced vasodilatation in the collared vascular bed was no longer differ ent from the vasodilatation in the control bed. Therefore, a developin g neo-intima reduces the blood flow through the collared carotid arter y before any morphological changes are detected. These results suggest that the nitric oxide-mediated dilator function of resistance vessels distal to the developing lesion is compromised, in this study in the absence of hyperlipidaemia.