Impairment of endothelium-dependent relaxation of aortas and pulmonary arteries from spontaneously hyperlipidemic mice ( Apodemus sylvaticus)

Abstract

We evaluated the endothelial function of thoracic aortas and pulmonary arteries in a population of European wood mice ( Apodemus sylvaticus), which exhibit hypercholesterolemia. According to the plasma cholesterol level, mice were divided into two groups: hypercholesterolemic (AHL, total plasma cholesterol 200–300 mg/dl) and normocholesterolemic (ANL, total plasma cholesterol < 200 mg/dl). Acetylcholine (ACh) caused endothelium-dependent relaxation of precontracted aortas and pulmonary arteries. Relaxation of the pulmonary artery is completely dependent on nitric oxide. This relaxation was inhibited in AHL pulmonary arteries. On the other hand, part of the ACh-induced relaxation of the thoracic aorta was resistant to N ω-nitro- l-arginine ( l-NNA). l-NNA-sensitive and -resistant relaxation to ACh were also inhibited in AHL aortas. Inhibition of endothelium-dependent relaxation of the aortas was correlated with total plasma cholesterol level. Endothelium-independent relaxation to sodium nitroprusside (SNP) was similar in AHL and ANL pulmonary arteries, but in the thoracic aorta of AHL mice, the sensitivity to SNP was slightly decreased, without a change in maximal response to SNP. No morphological change was observed in the aortas and the pulmonary arteries from AHL and ANL mice. Thus, AHL mice are valuable as a new experimental model to study the relation of hyperlipidemia to vascular disease since the endothelial function is impaired in these mild hyperlipidemic animals.