Prolonged hypercholesterolemia induces reversible alterations in venous vasomotor function.

Abstract

Hypercholesterolemia is associated with altered arterial endothelial and smooth muscle cell function. This study examines the influence of hypercholesterolemia on external jugular venous endothelial and smooth muscle cell vasoreactivity. Eighteen New Zealand White rabbits received a 1% cholesterol diet: in nine animals, this diet was continued until harvest at 8 weeks (hypercholesterolemic group), but in the other nine animals, the diet was changed to standard rabbit chow after 4 weeks and continued for a further 4 weeks (cholesterol reduction group). The change in the diet resulted in a 70% decrease in serum cholesterol concentration. Eight animals received standard rabbit chow for 8 weeks. Hypercholesterolemia induced hypersensitivity and increased maximal contractions to norepinephrine and endothelin-1. In addition, the maximal response to bradykinin increased, and a contraction to serotonin was induced in the veins from the hypercholesterolemic animals. Cholesterol reduction induced bradykinin hypersensitivity but had no effect on endothelin-1 sensitivity. Norepinephrine hypersensitivity returned to normal and the serotonin response disappeared. A decrease in the maximal contractile responses to these agonists was also observed. Hypercholesterolemia interfered with dose-dependent, EDRF (endothelium derived relaxing factor)-mediated relaxation induced by acetylcholine but, following the reduction of serum cholesterol, normal acetylcholine-induced, endothelium-dependent relaxation returned. Non-endothelium-dependent relaxation to sodium nitroprusside of precontracted veins was unaffected by the presence of high cholesterol concentrations. There were no morphological changes apparent in the veins of either the hypercholesterolemic or the cholesterol reduction groups. In conclusion, this study suggests that hypercholesterolemia induces reversible functional abnormalities in venous tissue and this ability of the jugular veins to recover may be, in part, linked to the lack of morphological changes.