EFFECT OF OBESTATIN ON CARDIOVASCULAR SYSTEM IN TYPE II DIABETIC RAT MODEL

Abstract

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.
Key words: Obestatin, type II diabetic rats, propranolol, prazocin, isolated thoracic aorta.