Metabolic Surgery Ameliorates Blood Pressure Through Antagonizing Overdrive Of The Sympathetic Nerve In Spontaneously Hypertensive Rat

Backgrounds and objectives:Hypertension is a major chronic disease endangering human health. Millions of people died due to the high blood pressure and its related heart, brain and ki dney complications every year. Long-term drug therapy and complications treatment brought great economic burdens to the patients and society. When hypertension combines with obesity or type 2 diabetes, it needs more kinds of drugs. But the therapeutic effect is not very good. Some clinical studies show that blood pressure can be effectively controlled after metabolic surgery. However, the precise mechanism is not clear. Further research of the mechanism may provide a new therapeutic strategy for the treatment of resistant hypertension.Bariatric surgery, also called metabolic surgery, can induce substantial and sustained weight loss and is a highly effective treatment for severe obesity and type 2 diabetes. A substantial number of clinical and experimental studies show that gastrointestinal intervention also resolve hypertension and improve the prognosis of cardiovascular events. The underlying mechanisms isn’t clear, although several mechanisms such as metabolic surgery-induced weight loss, changes in gut hormones and increased urinary sodium excretion have been postulated.To identify the mechanisms that metabolic surgery ameliorates hypertension, we studies whether metabolic surgery could ameliorate hypertension and attenuate cardiovascular remodeling and dysfunction by adoptting spontaneously hypertensive rats(SHR) and physiological and neurobiological means.Materials and methods:Eight-week-old male spontaneously hypertensive rats(SHR) were obtained from Charles Rivers Laboratories(Bar Harbor, ME). Rats were housed under a 12 h/12 h day/night cycle with free access to food and water. The institute’s Animal Care and Use Committee approved all animal protocols. The rats were randomly assigned to either Roux-en-Y gastric bypass(Surgery) or sham surgery-group(Sham). A subgroup of sham SHR was restricted and consumed 30% less chow than other sham SHR. There were 12 animals in each group. Detected the index after surgery as follows:1. BP and HR were measured after metabolic surgery by telemetry in conscio us and unrestrained rats.2. Vascular constriction were measured after metabolic surgery by freshly isolated arteries was studied by myograph system. Mesenteric vascular were obtained and stained with Hematoxylin-Eosin(H&E).3.Cardiovascular remodeling and heart function were measured after metabolic surgery by Hematoxylin-Eosin(H&E) and Masson’s Trichrome pathological staining. Echocardiography was performed with the Visual SONICS Ve Vo 770 imaging system.4. Renal sympathetic nervous activity(RSNA) and baroreflex were measured by NTS microinjection and sympathetic nerve discharge detection.Results:1. BP and HR was significantly lower in surgery group SHR compared with sham group(P<0.01).2. Small vascular diameter was significantly larger and vascular walls was significantly thinner in surgery group SHR compared with sham group and(P<0.01). ACh-elicited relaxation was obviously impaired in resistance arteries in surgery group SHR compared with sham group(P<0.01).3. Heart weight and myocardial collagen volume fraction were significantly reduced in SHR with surgery, compared to sham SHR(P<0.05). LVID and mitral valve E/A ratio increased as well as IVST and LVPW thickness decreased in SHR with surgery compared with sham SHR by M-mode echo-cardiography images analysis(P<0.05).4. The basal RSNA was lower in SHR with surgery compared with sham SHR(P <0.01). EFS induced a frequency-dependent contractile response which was significantly lower in isolated vascular segments from SHR with surgery compared with sham SHR(P<0.01). Microinjection of GABA into nucleus of the solitary tract(NTS) significantly reduced changes of artery blood pressure in SHR with surgery compared with sham SHR(P<0.05).5. Weight loss caused by dietary restriction didn’t affect the BP, HR and RSNA in sham SHR.Conclusions:Metabolic surgery ameliorates hypertension in spontaneously hypertensive rats and improves cardiovascular remodeling and dysfunction through inhibition of both peripheral and central sympathetic nerve activity.