Nitric oxide deficiency induces myocardial infarction in hypercholesterolaemic stroke-prone spontaneously hypertensive rats.
1. To observe the effect of nitric oxide (NO) on the myocardium, the NO synthesis inhibitor NG-nitro-L-arginine (L-NNA) was administered to hypercholesterolaemic stroke-prone spontaneously hypertensive (SHRSP) rats. 2. Hypercholesterolaemic SHRSP were produced by feeding SHRSP a high fat and high cholesterol diet (HFC) for 2 weeks. The rats were then divided into three groups: (i) the N group, which were fed the HFC diet containing 0.023% L-NNA and 1% NaCl in their drinking water (n = 10); (ii) the NH group, which were fed the HFC diet containing 0.023% L-NNA and 1% NaCl in their drinking water which also contained 80 mg/L hydralazine (n = 10); and (iii) the C group, which were fed the HFC diet and 1% NaCl in their drinking water (n = 10). 3. All rats in the N and NH groups died within 35 days of the initiation of L-NNA administration. Rats in the N and NH groups had significantly increased serum creatine phosphokinase, lactate dehydrogenase, glutamic oxaloacetic transaminase and serum total cholesterol levels compared with rats in the C group. 4. Fibrosis in response to necrosis was histopathologically observed in the hearts of all rats in the N and NH groups without exception. Occlusion or intimal thickening in the arteries adjacent to the necrotic regions was also observed. 5. These results suggest that nitric oxide deficiency induces myocardial infarction in hypercholesterolaemic SHRSP. These NO-deficient hypercholesterolaemic SHRSP offer a new model of myocardial infarction in rats.
Ikeda
K
K
Otsuka Department of International Preventive Nutritional Medicine, Graduate School of Human and Environmental Studies, Kyoto University, Japan. ikeda@helios.jinkan.kyoto_u.ac.jp.
Nara
Y
Y
Tagami
M
M
Yamori
Y
Y
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002561:Cerebrovascular Disorders / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D003331:Coronary Vessels / Q000187:drug effects / Q000473:pathology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005355:Fibrosis; D006830:Hydralazine / Q000494:pharmacology; D006937:Hypercholesterolemia / Q000150:complications*; D008297:Male; D009203:Myocardial Infarction / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D009206:Myocardium / Q000473:pathology; D009336:Necrosis; D009569:Nitric Oxide / Q000037:antagonists & inhibitors*; D019335:Nitroarginine / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR
D004791:Enzyme Inhibitors; D019335:Nitroarginine; D006830:Hydralazine; D009569:Nitric Oxide