Effects of a high-cholesterol diet on arterial wall thickness and vascular reactivity in young rabbits

Summary Cholesterol enrichment of arteries may induce biochemical and structural abnormalities in vascular smooth muscle resulting in increased arterial contractile sensitivity. We studied the effects of a high-cholesterol diet on arterial structural properties and vascular reactivity in young rabbits. In vivo measurements of aortic intimal-plus-medial thickness using high resolution ultrasound imaging were obtained before and after 3 weeks of a high-cholesterol diet in 12 rabbits (group 2) and compared to data from 12 animals a cholesterol-free diet fed (group 1). Six rabbits (group 3) were studied before and after a 3-week, high-cholesterol diet and after a subsequent 13-week, cholesterol-free recovery diet. Blood pressure responsiveness to noradrenaline was evaluated before and at the end of each diet period. In groups 2 and 3, high dietary cholesterol caused an increase in intimal-plus-medial thickness from 0.31 mm and 0.33 mm to 0.88 mm and 0.89 mm, respectively (p<0.001). Plasma cholesterol concentration rose from 0.9 ±0.26 mmol/l to 36.7 ± 8.56 mmol/l. There was no change in group 1. In group 3, intimal-plus-medial thickness remained increased (1.01 mm) following the cholesterol-free recovery diet despite normal plasma cholesterol. Blood pressure responsiveness to noradrenaline was markedly increased after the high-cholesterol diet (p<0.001) in groups 2 and 3 and after the cholesterol-free recovery diet in group 3 (p<0.001), and was directly related to intimal-plus-medial thickness (r=0.84;p<0.001). The data indicate that short-term high dietary cholesterol in the early life of rabbits causes long-lasting biochemical and structural arterial wall abnormalities, which might not only explain the observed increase in blood pressure responsiveness to noradrenaline, but could also lead to persistent functional vascular smooth muscle alterations. The result may be a predisposition to increased vascular smooth muscle response to high dietary cholesterol in adult life and development of high blood pressure and atherosclerosis.Abbreviations P_art mean arterial pressure - ACAT acyl-CoA-cholesterol-acyl-transferase - EDRF endothelium-derived relaxing factor - EDCF endothelium-derived contracting factor - NA noradrenaline