Effect of high-fat diet feeding on hypothalamic redox signaling and central blood pressure regulation.

We examined the effect of high-fat (HF) feeding on blood pressure (BP) regulation, including hypothalamic redox signaling, as well as the changes in diurnal patterns and responses to restraint stress. Furthermore, we investigated whether HF feeding affects catecholamine and neuropeptide Y (NPY) biosynthesis in the adrenal medulla. Male obesity-prone Sprague-Dawley rats were fed with standard rat chow or 60% HF diet for 6 months. BP and heart rate (HR) were measured by telemetry, and circadian changes as well as responses to 20 min restraint stress were analyzed. Mean arterial BP was significantly elevated in HF rats both during daytime and nighttime compared with controls, whereas HR was elevated only during the day. BP and HR increased similarly in response to stress in both experimental groups; however, post-stress recovery of BP and HR were significantly delayed in HF animals. Protein levels of angiotensin II type 1 receptor (AT(1)) and NOX2, p67(phox) and p47(phox) subunits of NADPH oxidase, as well as NADPH oxidase activity increased significantly in the hypothalamus with HF feeding, whereas levels of antioxidant enzymes and nitric oxide synthases remained unchanged. In addition, HF diet also elevated the adrenomedullary protein levels of tyrosine hydroxylase and NPY. This study shows that feeding obesity-prone Sprague-Dawley rats with a HF diet results in elevated BP and HR and delayed cardiovascular post-stress recovery, and that these changes are paralleled by increases in the expression and activity of NADPH oxidase in the hypothalamus without a compensatory increase in the antioxidant enzyme levels, possibly leading to superoxide-mediated sympathoexcitation and hypertension.