Reduced reactive oxygen species generation in rostral ventrolateral medulla suppresses the pressor response induced by the excitation of the paraventricular nucleus of the hypothalamus in spontaneously hypertensive rats

Abstract

BackgroundIncreased generation of reactive oxygen species (ROS) in the rostral ventrolateral medulla (RVLM) contribute to the neural mechanism of hypertension. The RVLM receives excitatory synaptic inputs from the paraventricular nucleus (PVN). It is also suggested that the angiotensin II type 1 receptors in the RVLM are activated by the PVN stimulation. Therefore, we examined whether the excitatory synaptic inputs derived from the PVN mediate the ROS in the RVLM or not.Methods and ResultsWe used 14 to 18‐week‐old male Wistar‐Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). We transfected adenovirus vectors encoding manganese superoxide dismutase gene (AdMnSOD) into the bilateral RVLM. Then, we microinjected bicuculline (BIC) (100pmol) into the unilateral PVN on day 7 after gene transfer. Microinjection of BIC into the PVN increased mean arterial blood pressure (MAP) in both SHR and MnSOD‐transfected SHR, however, the pressor response was significantly attenuated in MnSOD‐transfected SHR (SHR: 33±2 mmHg; MnSOD‐transfected SHR: 20±1 mmHg, n=5, P<0.05). Overexpression of MnSOD in the RVLM did not suppress BIC‐elicited MAP elevation in WKY rats (WKY rats: 14±1 mmHg; MnSOD‐transfected WKY rats: 13±1 mmHg, n=3).ConclusionExcitatory synaptic inputs arising from activation of the PVN to the RVLM are mediated, at least in part, by ROS generation in SHR, but not in WKY.