Renal Sympathetic Nerve Responses to Tempol in Spontaneously Hypertensive Rats

Abstract

Recent studies have implicated a contribution of oxidative stress to the development of hypertension. Studies were performed to determine the effects of the superoxide dismutase (SOD) mimetic 4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl (Tempol) on vascular superoxide production and renal sympathetic nerve activity (RSNA) in anesthetized Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). Compared with WKY rats (n=6), SHR showed a doubled vascular superoxide production, which was normalized by treatment with Tempol (3 mmol/L, n=7). In WKY rats (n=6), Tempol (30 mg/kg IV) significantly decreased mean arterial pressure (MAP) from 108+/-5 to 88+/-6 mm Hg and HR from 304+/-9 to 282+/-6 beats/min. In SHR (n=6), Tempol significantly decreased MAP from 166+/-4 to 123+/-9 mm Hg and HR from 380+/-7 to 329+/-12 beats/min. Furthermore, Tempol significantly decreased RSNA in both WKY rats and SHR. On the basis of group comparisons, the percentage decreases in MAP (-28+/-4%), HR (-16+/-3%) and integrated RSNA (-63+/-6%) in SHR were significantly greater than in WKY rats (-17+/-3%, -9+/-2%, and -30+/-4%, respectively). In SHR, changes in integrated RSNA were highly correlated with changes in MAP (r=0.85, P<0.0001) during administration of Tempol (3, 10, and 30 mg/kg IV). In both WKY rats and SHR (n=4, respectively), intracerebroventricular injection of Tempol (300 micro g/1 micro L) did not alter MAP, HR, or RSNA. Intravenous administration of a SOD inhibitor, diethyldithio-carbamic acid (30 mg/kg), significantly increased MAP, HR, and integrated RSNA in both WKY rats and SHR (n=6, respectively). These results suggest that augmented superoxide production contributes to the development of hypertension through activation of the sympathetic nervous system.

Increased Reactive Oxygen Species in Rostral Ventrolateral Medulla Contribute to Neural Mechanisms of Hypertension in Stroke-Prone Spontaneously Hypertensive Rats

“…Previous studies reported that intracerebroventricular infusion of tempol did not alter blood pressure in SHR. 13 Zanzinger et al, 17 however, demonstrated that chronic oxidative stress in the RVLM increases sympathetic nerve activity, suggesting that this site plays an important role in modulating sympathetic nerve activity by an increase in ROS.…”

“…11 Furthermore, intravenous infusion of tempol decreases blood pressure, and these effects are mediated by the inhibition of renal sympathetic nerve activity. 12,13 Among the target organs of hypertensive vascular diseases, the brain is most affected by aging and oxidative stress. 14,15 The brain contains a high concentration of polyunsaturated fatty acids in its cell membranes.…”

Redox Control of Renal Function and Hypertension

“…ET-1 was shown to be important in O 2 иϪ production in the sympathetic neurons of DOCAsalt hypertensive rats, and this was mediated by upregulation of ET (B) receptors (46). Renal sympathetic nerves respond to tempol by ameliorating elevation of high blood pressures in SHRs by decreasing oxidative stress (304). Longterm antioxidant treatment improves sympathetic functions and the ␤-adrenergic pathway in the SHRs (80).…”

Activation of Vascular BK Channel by Tempol in DOCA-Salt Hypertensive Rats

“…1 4-Hydroxy 2,2,6,6,-tetramethyl piperidine 1-oxyl (tempol), a superoxide dismutase (SOD) mimetic, lowers blood pressure in normotensive and hypertensive rats by multiple mechanisms. [2][3][4][5] Acute tempol treatment of normotensive, DOCA-salt and spontaneously hypertensive rats (SHRs) inhibits sympathetic nerve activity and this effect is not prevented by nitric oxide synthase (NOS) inhibition. [2][3][4][5][6] Local application of tempol onto renal sympathetic nerves decreased nerve activity without changing blood pressure (BP) or heart rate (HR).…”