Objectives: The present work was designed to studythe role of endocannabinoid system in the obesity associated atherogenesis and trying to clarify its possible mechanism/s of action. Methods: Thirty adult male wistar albino rats were utilized in the present experiment. They were divided into three equal groups (10 rats each); Group 1: Lean control group, which were fed normal laboratory chow diet and gavaged once daily by dimethyl sulfoxide in a dose of 0.6ml/kg /day for 10 weeks. Group 2: Atherogenic diet group which were fed high fat diet and gavaged once daily by dimethyl sulfoxide as group 1. Group 3: Atherogenic diet treated group which were fed high fat diet and gavaged once daily by NIDA-41020 (a selective cannabinoid receptor 1 blocker) in a dose of 10mg/ kg /day for 10 weeks. Then body mass index (BMI), bleeding time, and total clotting time were assessed. After that, the animals were sacrificed and lipid profile, atherogenic index, bleeding time, platelet aggregation percentage, clot retractions, clotting time, prothrombin time (PT), activated partial thromboplastin time (aPTT), total & differential leukocytic counts and serum adiponectin levels were assessed in all groups. The aorta was obtained from each animal dissected and stained by haematoxylin/eosin and oil Red O staining for histological examination and detection of aortic thickness and foam cells deposition. Results: The laboratory investigations and histological examination revealed, significant increases in BMI, lipid profile, atherogenic index, platelet aggregation%, peripheral monocytic count, and aortic thickness in the high fat diet received group versus lean controls which were otherwise associated with significant decreases in total clotting time, PT, aPTT, serum HDL & adiponectin levels. These changes were significantly and profoundly inhibited by the administration of the cannabinoid receptor antagonist. Conclusion: The endocannabinoid system is involved in the atherogenic changes associated with obesity. These effects were attributed to interference with serum adiponectin level, dyslipidemia, hypercoagulability, increased platelet activation & peripheral as well as endothelial recruitment of monocytes. These effects were found to be via activation of cannabinoid 1 receptor.
Background: Obestatin (OB) is a novel anorexiogenic peptide produced in the stomach. It has been shown to regulate glucose and lipid metabolism. However, its potential role in cardiovascular control is still not clear and controversial. Aim of the work: To evaluate the in vivo and in vitro effects of Obestatin on cardiovascular system in both normal and diabetic rats. Also, to identify the possible mechanism of its action. Material and methods: 40 healthy male albino rats weighing 180-200 gm. were used and divided into two main groups: In vivo experiments subdivided into normal (n= 10) and Type II Diabetes induced groups (n=10) In which heart rate and blood pressure were recorded before and after OB (100 Mg/kg body weight) injection , In vitro experiments subdivided into normal (n= 10) and Type II Diabetes induced group (n= 10) in which the effect of OB (1 nmol/l) alone and its effect in presence of β-blocker propranolol (30Mmol/l) and α blocker prazosin (3Mmol/l) on amplitude and frequency of cardiac contractility were studied ,also effects of OB alone (100 pmol/l) and in presence of LNAME(0.3Mmol/l) on contraction induced by phenylephrine (10 Mmol/L) of isolated thoracic aorta. Type II Diabetes induced by feeding rats for two weeks a high-fat diet (58% fat, 25% protein, 17% carbohydrates as percentage of total calories). On day 13, rats were given a single intraperitoneal injection of streptozotocin (25 mg/kg body). Results: Obestatin injection showed no significant difference on blood pressure and heart rate in both normal and diabetic rats, However in vitro studies showed that OB has both positive inotropic and chronotropic effects on isolated heart of both normal and diabetic rats which were blocked by propranolol but not by prazocin. Moreover, OB produced significant vascular relaxation of isolated rat thoracic aorta of the normal group which was attenuated by L-NAME in normal rats. However, the relaxation effect of OB was much weaker in diabetic rats and was blocked by L-NAME. Conclusion: Obestatin improves cardiac function and exerts vasodilator effects via nitric oxide (NO) release, so it may be decrease systemic vascular resistance in type II diabetes.
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