The Effect And Mechanism Of Bariatric Surgery On Blood Pressure In Spontaneously Hypertensive Rats

Background:Bariatric surgery can effectively improve the body weight of morbidly obese patients,and also has some therapeutic effects on metabolic complications such as hypertension.In recent years,it has been found that bariatric surgery can reduce blood pressure in essential hypertension patients and rats.It has also been found that bariatric surgery can improve the endocannabinoid system.The endocannabinoid system is closely related to cardiovascular,immune,analgesic function and energy metabolism,and can especially improve the contractile function of the heart and blood vessels,so as to control the blood pressure.Therefore,we hypothesized that the endocannabinoid system may be involved in the hypotensive effects of bariatric surgery in essential hypertension patients and rats.In this study,through the establishment of total gastrectomy with Roux-en-Y reconstruction and duodenal jejunal bypass models,we researched the effect of different operation models in blood pressure,heart function,endocannabinoids and their receptors in primary hypertension rats,and explored the possible mechanisms of its hypotensive effects.Methods:Forty spontaneously hypertension rats were divided into four groups randomly:total gastrectomy with a Roux-en-Y reconstruction group(RYTG,n=10),duodenal-jejunal bypass group(DJB,n=10),sham operation group(SO,n=10),and non-operated control group(NC,n=10).Body weight and blood pressure were consistently measured before and one week,two weeks,four weeks,six weeks and eight weeks after surgery.Echocardiography,plasma and tissues endocannabinoid levels as well as cannabinoid receptor type 1(CB1)were evaluated eight weeks postoperatively.Results:Compared with DJB and SO groups,total gastrectomy with Roux-en-Y reconstruction could decreased body weight in spontaneous hypertension rats.Eight weeks after surgery(296.8±8.9 vs.DJB group 328.6±12.4 g,P<0.001)and(296.8±8.9 vs.SO group 334.0±10.3 g,P<0.001).Blood pressure also decreased significantly.Systolic blood pressure compared with DJB group at six weeks after operation was(182.4±10.9 vs.196.4±11.2 mmHg,P=0.005),at eight weeks(180.5±14.7 vs.198.4±10.0 mmHg,P=0.002);compared with SO group at six weeks after operation(182.4±10.9 vs.193.3±13.9 mmHg,P=0.014),at eight weeks(180.5±14.7 vs.198.1±9.8 mmHg,P=0.002).While there was no significant difference between the three groups in diastolic blood pressure,so systolic blood pressure was better than diastolic blood pressure.Eight weeks postoperatively,heart rate,stroke volume,cardiac output and fractional shortening of rats decreased in the total gastrectomy with Roux-en-Y reconstruction group,left ventricular internal diameter of systole increased,while ejection fraction,left ventricular wall thickness and ventricular septal thickness had no obvious improvement.There was no statistical difference among the other three groups.The level of endocannabinoid in myocardium of rats in total gastrectomy with a Roux-en-Y reconstruction group was increased,especially anandamide(AEA)and 2-arachidonoylglycerol(2-AG),AEA level(0.108±0.007 vs.NC group 0.070±0.005 pmol/mg,P<0.001;vs.SO group 0.0761±0.003 pmol/mg,P<0.01;vs.DJB group 0.084±0.006 pmol/mg,P<0.05),2-AG level(0.836±0.030 vs.NC group 0.395±0.016 pmol/mg,P<0.001;vs.SO group 0.542±0.053 pmol/mg,P<0.001;vs.DJB group 0.603±0.039 pmol/mg,P<0.05)with its receptors increasing.However,there was no significant changes in the duodenum jejunum bypass group and sham operation group.In the hypothalamus,duodenum and jejunum,the levels of endocannabinoid and its receptor also changed.Plasma endocannabinoid levels has no statistical difference among the four groups.Conclusion:Compared with duodenal-jejunal bypass,total gastrectomy with Roux-en-Y reconstruction can significantly improve the blood pressure and cardiac function in spontaneous hypertension rats.The mechanism is that the level of endocannabinoid and its receptor in myocardium is increased after total gastrectomy with Roux-en-Y reconstruction,which can inhibit the sympathetic activity,so as to improve the cardiac function and decline the blood pressure.