الفهرس 
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Abstract
Nitric oxide ”NO” considered as one of the endothelium-derived relaxing factor which cause relaxation of smooth muscles of blood vessels. NO causes dilation of blood vessels and so blood easily to flow. Isosorbide dinitrate ”ISDN”, an organic nitrate that able to generate NO in cells and used for treating angina and heart diseases. Hyper-cholesterolemia ”high blood total cholesterol” decreases the level of NO and causes atherosclerosis.
So the present study aims to investigate the role of ISDN on the disturbance induced by hypercholesterolemia via the generation of NO.
Eighty four male rats were used in the present study, divided into six groups (14 animals each) fed on standard diet and supplied with water ad libitum:
First group ”control group” normal untreated rats.
Second group ”coconut oil group” treated daily with 0.5ml coconut oil for 3 weeks.
Third group ”cholesterol group” treated daily with cholesterol {400 mg / kg b.w dissolved in 0.5 ml coconut oil} for 3 weeks.
Fourth group ”ISDN group” treated daily with ISDN {1.0 mg / kg b.w dissolved in 0.5 ml H2O} for 3 weeks.
Fifth group ” ISDN with cholesterol group” treated daily with ISDN {1.0 mg / kg b.w dissolved in 0.25 ml H2O} and cholesterol {400 mg / kg b.w dissolved in 0.25 ml coconut oil} for 3 weeks.
Sixth group ”ISDN after cholesterol group” treated daily with cholesterol {400 mg / kg b.w dissolved in 0.5 ml coconut oil} for 3 weeks then treated daily with ISDN {1.0 mg / kg b.w dissolved in 0. 5 ml H2O} for other 3 weeks. All treatments were carried out by gastric intubation.
The study includes determination of:
(1) Weight Gain % and Relative Organ Weights
The fifth and 6th groups showed significant decrease and increase respectively in percentage of weight gain when compared to the control group. Liver relative weight increased significantly with coconut oil treatment. Relative weight of heart, lung, liver and kidney showed significant increases in cholesterol treated group. The 5th and 6th treated groups showed significant increases in lung and kidney relative weights.
(2) Haematological Parameters
Haemoglobin content and haematocrit value showed significant increases in ISDN treated group compared to control and other treated groups. Mean corpuscular haemoglobin ”MCH” increased significantly in the 5th and 6th groups. ISDN after cholesterol showed significant increase in platelets count.
(3) Respiratory Functions of Blood
Cholesterol and ISDN treatment induced respiratory alkalosis which indicated by an increase in blood pH and decrease in arterial blood carbon dioxide partial pressures ”PaCO2 mmHg”. ISDN induced significant increase in oxygen content in arterial and venous blood. The 5th and 6th groups showed significant decreases in oxygen carrying capacity and oxygen content as compared to the control group. Coconut oil, cholesterol and ISDN treated groups showed non significant increases in P50 but the 5th and 6th groups showed non significant decreases when compared with the control group. The Hill´s coefficient (n value) showed significant decreases in all treated groups except ISDN with cholesterol treated group which showed significant increase when compared to the control one.
(4)Biochemical Parameters
(a)Nitric oxide and antioxidant enzymes:
Serum nitric oxide level showed significant decrease with cholesterol treatment and increase with ISDN treatment. Superoxide dismutase decreased in all treated groups except in ISDN group where it increased, while glutathione peroxidase showed decreases in all treated groups when compared to the control group.
(b) Serum lipid profile:
Coconut oil treated group showed significant increases in high density lipoprotein cholesterol ”HDL-C” and very low density lipoprotein cholesterol ”VLDL-C”. Total cholesterol and low density lipoprotein cholesterol ”LDL-C” increased significantly with cholesterol treatment. ISDN treated group showed significant increases in triglycerides and VLDL-C and significant decreases in LDL-C. ISDN with cholesterol treatment showed significant increases in LDL-C. ISDN after cholesterol treatment induced non significant change in lipid profile as compared to the control group.
(c) Serum glucose, total protein, albumin and uric acid:-
Serum glucose level decreased in cholesterol treated group. Albumin increased significantly in ISDN treated group. Total protein and uric acid showed non significant changes in all treated groups.
(5) Immunological Parameters
Coconut oil treatment induced significant decreases in neutrophils and monocytes percentage. White blood cells ”WBCs” count and neutrophils percentage increased significantly with cholesterol treatment while lymphocytes and platelets decreased. WBCs showed a significant increase with ISDN treatment. The 5th group showed significant increase and decrease in percentage of neutrophils and lymphocytes respectively. ISDN after cholesterol showed a significant decrease in neutrophils percentage. Serum total globulins showed non significant changes in all treated groups. Alpha globulin showed non significant difference between groups. Beta globulin showed a significant increase in 6th group. Gamma globulin increased significantly in ISDN treated group.
(6) Corticosterone and Testosterone
All treated groups showed non significant increases in serum corticosterone and testosterone levels as compared to the control group.