Off-target effects of sleeve gastrectomy on blood pressure independent of body weight reduction in diet-induced obesity rats: role of cholecystokinin

Objective: Sleeve gastrectomy (SG) is currently the most selected surgical bariatric procedure for weight loss by shrinking the stomach. SG has been reported to improve glucose metabolism by altering gastrointestinal hormones, but the details of why blood pressure improves are not known. The purpose of this study is to elucidate the mechanism of why SG lowers blood pressure in diet induced obese rats. Design and method: Male Sprague Dawley (SD) rats were subjected to surgical [sham operation (SO) or SG] and dietary interventions [fed a normal diet or high fat diet (HFD) ad libitum or pair fed (PF)]. Diet induced obese rats fed 60% HFD for 12 weeks. Systolic blood pressure (SBP), urinary sodium excretion, and gastrointestinal hormones and renin angiotensin system in renal tissue were examined 4 weeks after surgery. In addition, cholecystokinin (CCK) was administered intraperitoneally to SD rats and evaluated for changes in blood pressure and renal tissue renin angiotensin system. Results: Both SG and PF treatments reduced body weight compared with SO. SG exhibited a reduction in SBP compared with PF, which was associated with a reduction in renal renin (536 ± 48.5 U/g kidney and 1385 ± 55.1 U/g kidney, p < 0.01), angiotensin II (Ang II) (48.2 ± 5.8 ng/g kidney and 258.7 ± 16.9 ng/g kidney, p < 0.01), and catechol O methyltransferase (COMT) levels (0.68 ± 0.05 /αtub and 1.34 ± 0.13/αtub, p < 0.01). SG increased plasma CCK levels compared with PF (p < 0.01 for each), whereas GLP1 and PYY were not changed in fasting. SD rats after CCK administration showed decreased SBP (107.7 ± 2.3 mmHg and 118.0 ± 1.8 mmHg, p < 0.01), COMT (0.49 ± 0.04 /GAPDH and 1.11 ± 0.19/GAPDH, p = 0.02), renin (967 ± 71.3 U/g kidney and 1394 ± 90.8 U/g kidney, p < 0.01), and Ang II (598 ± 76.7 ng/g kidney and 874 ± 86.6 ng/g kidney, p = 0.02) in the kidney compared to controls. Conclusions: The SG reduced SBP, at least in part, through suppression of the sympathetic nerve action by elevation of CCK which is followed by suppression of the intrarenal renin angiotensin system. Conclusions: CCK may have a blood pressure lowering effect, and further research is needed to determine whether CCK can be used as a new antihypertensive agent in the future.