Reduced Responsiveness of Hypercholesterolemic Rabbit Aortic Smooth Muscle Cells to Nitric Oxide

摘要: The response to nitric oxide of intracellular free Ca2+ levels, measured by fura 2 fluorimetry, and cyclic GMP, RIA, was evaluated on smooth muscle cells the thoracic aorta in primary culture from normal cholesterol-fed rabbits. Relaxation acetylcholine also determined isolated rings aorta. After 10 weeks high-cholesterol diet, intact relaxed less both oxide. In cultured hypercholesterolemic rabbits, oscillated, mean levels were approximately twofold greater than aortic cells. Nitric failed affect basal either cell type. peak sustained rise induced angiotensin II (10−7 mol/L) similar two types. However, (10−10 10−6 decreased a significantly smaller extent addition, added before inhibited degree transient increase caused nominal absence extracellular Ca2+, as well associated with addition Ca2+. Measurements quenching Mn2+ influx confirmed that entry divalent cations Basal GMP normal, increased These data indicate substantial resistance action This observation is consistent notion contributes abnormal endothelium-dependent vasodilatation during hypercholesterolemia can play role pathogenesis atherosclerosis.