Vertical sleeve gastrectomy (VSG) is a bariatric procedure that involves removal of approximately 80% of the stomach along the greater curvature. VSG leads to decreased body weight and adiposity as well as reduced hypertension. We have observed that VSG reduces blood pressure in rats maintained on high-fat diet (HFD), and that this effect is independent of body weight and obesity, by utilizing a pair-feeding paradigm. We examined potential mechanisms contributing to the reduced arterial pressure following VSG by investigating the effect of VSG on proposed mechanisms linking obesity to hypertension, including hyperactivity of the renin-angiotensin system (RAS), hyperinsulinemia, hyperlipidemia and hyperleptinemia. Male rats were fed an AIN93M HFD containing approximately 45% fat by kilocalories at a density of 4.73 kcal/g for 14 weeks prior to surgery. Rats were then allocated into three weight-matched groups to undergo the dual surgery: a blood pressure telemetry implant and either VSG or Sham surgery. Producing three groups 1) VSG, 2) Sham- ad libitum fed (AL) and 3) Sham-pair fed (PF). Arterial pressure was recorded continuously for 4 months and animals were given a number of pharmacological challenges to determine cardiovascular responsiveness following VSG surgery to acute injection of the beta-agonist isoproterenol, acute injection of the beta-antagonist propranolol and chronic L-NAME treatment. VSG led to significant reductions in arterial pressure relative to both sham-PF and sham-AL groups, all groups were similarly responsive to sympathetic manipulation and nitric oxide synthase inhibition. Plasma levels of triglycerides, non-esterified fatty acids, insulin and leptin were all similarly reduced in VSG and PF animals, relative to the AL group. However, activity of the RAS was lower only in the VSG group, suggesting that suppression of the RAS may be a major contributor to the reduction in hypertension following bariatric surgery.