The study was supported by Novartis.

The data suggest that the hypertension and sympathoexcitation in 2K-1C rats were associated with an increase in oxidative stress within the RVLM, the PVN and systemically.

There is increasing evidence to support the hypothesis that reactive oxygen species (ROS) play a role in the pathophysiology of arterial hypertension. The ROS, particularly the superoxide anions (O 2 − ), are important intracellular messengers for Angiotensin II (Ang II) action in the brain. Ang II increases the activity of NAD(P)H oxidase, the major source of O 2 − in the vasculature, and enhances O 2 − production, both systemically and in the central nervous system. 1,2,3 For instance, intracerebroventricular infusion of NAD(P)H oxidase inhibitor antagonizes the increase in renal sympathetic nerve activity (RSNA) and the pressor response induced by centrally mediated Ang II actions. 3,4 In the brain, overexpression of superoxide dismutase (SOD), the enzyme responsible for O 2 − breakdown, also abolishes the central pressor effect of the octapeptide. 5 There is evidence to suggest that the central nervous system is involved in the development and maintenance of arterial hypertension. 6 However, the precise mechanisms by which the central nervous system participates in the evolution of arterial hypertension remains unclear and depends on the specific origin and phase of the hypertensive state. It is well known that in the 2K-1C (two-kidney one-clip) Goldblatt hypertension, the rostral ventrolateral medulla (RVLM) is one of the most important regions involved in the hypertension. 7 Therefore, the first aim of the present study was to examine whether there is an increase in oxidative stress within the RVLM in 2K-1C hypertension. For this purpose, the NAD(P)H oxidase subunits (p47phox and gp91phox) and CuZnSOD mRNA expression were quantified in the RVLM of 2K-1C hypertensive rats.Tai et al. 8 found that in SHR, elevated O 2 − radical production in the RVLM was associated with increased sympathetic nervous system activity; however, this mechanism had not been tested in a renovascular hypertension model. The second aim of the present study was therefore to examine whether oxidative stress is involved in the maintenance of sympathetic vasomotor tone and hypertension in 2K-1C rats. For this purpose, we injected directly into the RVLM the antioxidant ascorbic acid (vitamin C-Vit C), that acts as a free radical Background Oxidative stress is a state in which excess reactive oxygen species (rOS) overwhelm endogenous antioxidant systems. It is known that this state has been involved in the development of hypertension. On the basis of previous data, we hypothesized that overactivity of naD(P)H oxidase-derived rOS and the lowered activity of CuZnSOD, an endogenous antioxidant within the rostral ventrolateral medulla (rVLM), could contribute to 2K-1C (two-kidney one-clip) hypertension. Moreover, to test the functional significance of whether oxidative stress was involved in the maintenance of sympathetic vasomotor tone and blood pressure in 2K-1C hypertension, we administered ascorbic acid (Vit C), an antioxidant, into the rVLM or systemically.

The aim of the present study was to examine the participation of the rostral ventrolateral medulla (RVLM) in the maintenance of hypertension in rats submitted to the renovascular Goldblatt (two-kidney, one clip) procedure. We inhibited or stimulated this area with the use of drugs such as glycine, L-glutamate, or kynurenic acid. (1) Bilateral microinjection of glycine (100 nmol, 200 nL, n = 13) into the RVLM of hypertensive rats produced a decrease in mean arterial blood pressure (MAP) from 177.2 +/- 29.3 to 102.3 +/- 20.9 mm Hg (P < .05), which was similar to the decrease produced by intravenous administration of hexamethonium. The inhibition of RVLM with glycine in normotensive rats produced a decrease in MAP from 106 +/- 17.1 to 59.7 +/- 7.3 mm Hg (P < .05, n = 9). (2) An impressive increase in MAP from 153.3 +/- 16.3 to 228 +/- 34.9 mm Hg (P < .05) occurred in hypertensive rats after microinjection of L-glutamate (50 nmol, 200 nL, n = 6) into the RVLM. The same procedure caused a significant but less intense increase in MAP from 105 +/- 13.8 to 148.3 +/- 24.9 mm Hg in normotensive rats (P < .05, n = 6). (3) A decrease in MAP from 151.6 +/- 25.3 to 96.8 +/- 22.5 mm Hg occurred in hypertensive rats after microinjection of the broad-spectrum glutamate antagonist kynurenic acid (4 nmol, 200 nL, n = 6) into the RVLM, whereas the same procedure did not change MAP in normotensive animals (n = 6). Heart rate was not significantly affected in any group.(ABSTRACT TRUNCATED AT 250 WORDS)

No abstract