Role of the Rostral Ventrolateral Medulla in the Arterial Hypertension in Chronic Renal Failure

Sympathetic activation in chronic renal failure (CRF) is a major mechanism leading to the progression of renal disease and hypertension. In the present study, we tested the hypothesis that in CRF increased reactive oxygen species (ROS) production in the RVLM mediated by enhanced circulating Angiotensin II (Ang II) is an important mechanism leading to hypertension in CRF. In CRF rats we found an increase in the abundance of p47phox and gp91phox mRNA within the RVLM associated with a reduction of Ang II type 1 receptors (AT1) mRNA in the brainstem compared to controls (C). Tempol but not candesartan into the RVLM decreased MAP in CRF but not in C rats. GABA into the RVLM decreased MAP in CRF ( ？mmHg) more intensely than in C ( ？mmHg). The results suggest that increased oxidative stress within the RVLM has an important participation to maintain hypertension in CRF rats apparently independently of AT1 Ang II receptors. 1. Introduction The chronic renal failure (CRF) is characterized by high circulating Angiotensin II (Ang II) that causes direct vasoconstriction, increases aldosterone secretion, enhances sympathetic nerve activity, and increases reactive oxygen species production (ROS), acting at peripheral and central sites [1]. There is increasing evidence to support the hypothesis that ROS play a major role in the pathophysiology of CRF [2]. In fact, Ang II action in the brain increases the activity of NAD(P)H oxidase, a major source of superoxide anion (O2) production [2]. NAD(P)H oxidase is composed of two membrane-bound subunits (gp91phox and p22phox), several cytoplasmic units (p40phox, p47phox, and p67phox), and the small G protein Racla [3]. After activation of Ang II type 1 (AT1) receptors, the cytoplasmic subunits bind to the membrane subunits and activate the enzyme, resulting in the intracellular production of O2-？？[4]. Therefore, the first aim of the present study was to quantify the NADPH p47phox and gp91phox subunits expression within the RVLM. Considering that in CRF there is an increase in the brain Ang II, the expression of AT1 subtype receptor was also quantified in the RVLM. To functionally test the role of oxidative stress and AT1 receptors on hypertension in CRF rats we injected into the RVLM the superoxide mimetic-tempol and the AT1 antagonist-candesartan, respectively. Finally, the importance of RVLM in the maintenance of hypertension in CRF was evaluated by injection of GABA into the region. 2. Materials and Methods 2.1. General Procedures All experimental procedures were conducted according to the National Institutes of Health