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.
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.
Aliev
G
G
Laboratory of Electron Microscopy, Case Western Reserve University, Cleveland, Ohio 44106-4938, USA.
Shi
J
J
Perry
G
G
Friedland
R P
RP
Lamanna
J C
JC
D000818:Animals; D001011:Aorta / Q000166:cytology / Q000378:metabolism*; D001835:Body Weight; D002791:Cholesterol, Dietary / Q000494:pharmacology*; D019826:Cholic Acid / Q000008:administration & dosage / Q000494:pharmacology; D004032:Diet; D019332:Endothelin-1 / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D007150:Immunohistochemistry; D008055:Lipids / Q000097:blood; D008297:Male; D008854:Microscopy, Electron; D008855:Microscopy, Electron, Scanning; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D051381:Rats; D011919:Rats, Inbred Strains; D013889:Thiouracil / Q000008:administration & dosage / Q000494:pharmacology
D002791:Cholesterol, Dietary; D019332:Endothelin-1; D008055:Lipids; D013889:Thiouracil; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496322:Nos1 protein, rat; C496318:Nos2 protein, rat; C496316:Nos3 protein, rat; D019826:Cholic Acid