dizocilpine-maleate and Hypertension--Renovascular

Exercise training (ExT) has been reported to benefit hypertension; however, the exact mechanisms involved are unclear. We hypothesized that ExT attenuates hypertension, in part, through the renin-angiotensin system (RAS), reactive oxygen species (ROS), and glutamate in the paraventricular nucleus (PVN). Two-kidney, one-clip (2K1C) renovascular hypertensive rats were assigned to sedentary (Sed) or treadmill running groups for eight weeks. Dizocilpine (MK801), a glutamate receptor blocker, or losartan (Los), an angiotensin II type1 receptor (AT1-R) blocker, were microinjected into the PVN at the end of the experiment. We found that 2K1C rats had higher mean arterial pressure (MAP) and renal sympathetic nerve activity (RSNA). These rats also had excessive oxidative stress and overactivated RAS in PVN. Eight weeks of ExT significantly decreased MAP and RSNA in 2K1C hypertensive rats. ExT inhibited angiotensin-converting enzyme (ACE), AT1-R, and glutamate in the PVN, and angiotensin II (ANG II) in the plasma. Moreover, ExT attenuated ROS by augmenting copper/zinc superoxide dismutase (Cu/Zn-SOD) and decreasing p

Topics: Angiotensin II Type 1 Receptor Blockers; Animals; Disease Models, Animal; Dizocilpine Maleate; Excitatory Amino Acid Antagonists; Gene Expression Regulation; Glutamic Acid; Hypertension, Renovascular; Losartan; Male; NADPH Oxidase 2; NADPH Oxidases; Paraventricular Hypothalamic Nucleus; Peptidyl-Dipeptidase A; Physical Conditioning, Animal; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; Receptor, Angiotensin, Type 1; Receptors, Glutamate; Renin-Angiotensin System; Sedentary Behavior; Signal Transduction; Superoxide Dismutase