Abstract 1417: Contribution of Angiotensin II in the Increased Reactive Oxygen Species in Rostral Ventrolateral Medulla and Enhanced Central Sympathetic Outflow in Stroke-Prone Spontaneously Hypertensive Rats
Background: We demonstrated that reactive oxygen species (ROS) are increased in the rostral ventrolateral medulla (RVLM) in the brainstem, where the vasomotor center is located, in stroke-prone spontaneously hypertensive rats (SHRSP). The brain renin- angiotensin system plays an important role in the neural mechanism of hypertension. It is suggested that angiotensin II (Ang II) increases ROS production via the NADPH oxidase pathway, which is regulated by the small GTP-binding protein Rac1. The aim of the present study was to evaluate whether brain Ang II contributes to increase the ROS in the RVLM and to enhance central sympathetic outflow in SHRSP.
Methods: SHRSP were treated orally with telmisartan (10 mg/kg per day) for 30 days. In other SHRSP, we transfected adenovirus vectors encoding dominant-negative Rac1 (AdN17Rac1) into the RVLM to inhibit the NADPH oxidase/Rac1 pathway. Blood pressure and heart rate were measured. Urinary norepinephrine excretion was measured as a marker of sympathetic nerve activity. We measured ROS using the salicylate trapping technique to quantify 2,3-dihydrobenzoic acid by in vivo microdialysis. Levels of ROS in the RVLM of SHRSP were measured and compared with those of WKY. The changes of ROS levels in the RVLM were evaluated after treatment with telmisartan or transfection of AdN17Rac1. Furthermore, the effects of infusion of Ang II into the RVLM on blood pressure and ROS production were observed before and after treatment.
Results: Both treatment with telmisartan and transfection of AdN17Rac1 in RVLM decreased blood pressure, heart rate, and urinary norepinephrine excretion in SHRSP. ROS levels in the RVLM measured by in vivo microdialysis were greater in SHRSP than in WKY. ROS levels were decreased by treatment with telmisartan or transfection of AdN17Rac1 in SHRSP. Blood pressure and ROS production were increased during infusion of Ang II into the RVLM, and the increases in these variables were greater in SHRSP than in WKY. These effects were attenuated by both treatment with telmisartan and transfection of AdN17Rac1 in SHRSP.
Conclusions: These results suggest that brain Ang II contributes to increase the ROS in the RVLM of SHRSP and might also contribute to the activation of the central sympathetic outflow and hypertension.