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

Abstract

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.

Effect of age on high-fat diet-induced hypertension

“…HF diet did increase AT 1 receptor expression in both the hypothalamus and NTS in the two age groups, which corresponds with our previous findings (10). In addition, although there were agerelated differences in the upregulation of NADPH oxidase subunits (for example, hypothalamic NOX-2 and p47 subunits only elevated in young rats in response to HF feeding), NADPH oxidase activity elevated similarly in the two age groups.…”

“…Superoxide anion has been implicated in the mediation of sympathoexcitatory stimuli both in the hypothalamus and brain stem (11,17,27,44), and we have previously demonstrated that high-fat (HF) diet-induced obesity increased the expression and activity of NADPH oxidase, a major source of superoxide anion, in the hypothalamus, while antioxidant defense mechanisms remain unchanged (10). On the other hand, although aging does not increase central NADPH oxidase expression, it reduces hypothalamic expression of antioxidant enzymes such as copper-zinc superoxide dismutase and catalase, resulting in increased oxidative stress (13).…”

Protective effect of the daming capsule on impaired baroreflexes in STZ-induced diabetic rats with hyperlipoidemia

“…Both glutamate and GABA also play important roles in maintaining baroreflex sensitivity. The release of glutamate could decrease blood pressure through the action of glutamate on AMPA receptors containing GluR2 [24,25] while GABA increases blood pressure by inhibiting the parasympathetic system circuit via GABA A receptors [26,27]. Our findings suggested that the protective effects of DMC on baroreflex control of heart rate could be due to the upregulation of GluR2 and a concomitant increase in synaptic transmission or neuronal excitability within the baroreceptor reflex pathway.…”

Ivabradine reversed nondipping heart rate in rats with l‐NAME‐induced hypertension

“…Similar HR dip attenuation was previously found in spontaneously hypertensive rats 21 and high-fat diet-induced hypertension. 22 In hypertensive rats, ivabradine dosed at daytime (the rat's resting phase) reverted the night-to-day HR rise to HR dip by 14.2%; whereas the night-time-dosed ivabradine did not exert this beneficial effect, as it left the undesirable HR rise unchanged. Interestingly, in line with our previous results, both daytime-dosed and night-time-dosed ivabradine exerted an antihypertensive effect.…”