NOS uncoupling and redox‐dependent baroreflex inhibition in neural mechanism of metabolic syndrome‐associated hypertension

Abstract

Up to 75% of patients with metabolic syndromes also exhibit hypertension, although the underlying mechanism is not fully understood. Alterations in neural control of cardiovascular functions are evident in both disease conditions. We tested the hypothesis that oxidative stress because of nitric oxide synthase (NOS) uncoupling in the nucleus tractus solitarii (NTS), terminal sites of the baroreceptor afferents in the brain stem, is involved in the reduced baroreflex function and hypertension under metabolic syndromes. Normotensive Wistar‐Kyoto rats subjected to 8‐weeks high fructose (HF) diet developed hyperglycemia, hyperlipidemia, insulin resistance and hypertension, with concurrent increases in protein expression of neuronal and endothelial NOS (nNOS and eNOS), and a NOS inhibitor, asymmetric dimethylarginine (ADMA), as well as tissue levels of the reactive oxygen species (ROS) but not NO in NTS. Baroreflex sensitivity was significantly reduced in the animals; and was reverted by intracisternal infusion of a ROS scavenger, tempol, or an ADMA inhibitor, dimethylarginine dimethylaminohydrolase (DDAH). DDAH treatment also attenuated ROS production in NTS and promoted antihypertension in the experimental rats. These results suggest that increase in ROS production due to NOS uncoupling in NTS inhibits baroreflex sensitivity and promotes hypertension under metabolic syndromes.