Decreased constitutive nitric oxide synthase, but increased inducible nitric oxide synthase and endothelin-1 immunoreactivity in aortic endothelial cells of donryu rats on a cholesterol-enriched diet.

Abstract

The Donryu rat is resistant to a high cholesterol diet in that typical atheromatous lesions do not develop. Using electron microscopic immunocytochemical techniques, the effects of a CCT diet (4% cholesterol with 1% cholic acid and 0.5% thiouracil) on the distributions of neuronal, macrophage, and endothelial specific nitric oxide synthase (NOS I, NOS II, and NOS III) and endothelin-1 (ET-1) immunoreactivity were examined in the thoracic aortic intima. Atheromatous lesions were absent, but immunocytochemistry showed 1. 4+/-0.52% and 4.0+/-0.9% endothelial cells (EC) with positive staining for NOS I and NOS III, respectively, compared with 16.3+/-2. 5% and 88.6+/-2.48% in control Donryu rats. The CCT-supplemented diet induced expression of NOS II immunoreactivity in thoracic aortic intimal cells. EC, subendothelial macrophages, and smooth muscle cells (SMC) also showed high NOS II-positive staining. The percentage of NOS II-immunoreactive EC was 43+/-1.8%. In control groups, no NOS II immunoreactive cells were observed. The percentage of ET-1 immunopositive cells was also significantly increased by 9. 2+/-0.66% and 64.2+/-1.4% in control and CCT-fed groups, respectively. It is concluded that the administration of a high cholesterol diet in Donryu rats produces endothelial dysfunction associated with changes in the balance of the different isoforms of NOS and ET-1. Therefore, the increase in inducible NOS and ET-1 immunoreactivity seen during the cholesterol-enriched diet appears to be a compensatory reaction of aortic wall cells to the high cholesterol supplementation.