TY - JOUR
T1 - Systemic arterial pressure response to two weeks of Tempol therapy in SHR
T2 - Involvement of NO, the RAS, and oxidative stress
AU - Yanes, Licy
AU - Romero, Damian
AU - Iliescu, Radu
AU - Cucchiarelli, Valeria E.
AU - Fortepiani, Lourdes A.
AU - Santacruz, Francisco
AU - Bell, William
AU - Zhang, Huimin
AU - Reckelhoff, Jane F.
PY - 2005/4
Y1 - 2005/4
N2 - The roles of nitric oxide (NO) and plasma renin activity (PRA) in the depressor response to chronic administration of Tempol in spontaneously hypertensive rats (SHR) are not clear. The present study was done to determine the effect of 2 wk of Tempol treatment on blood pressure [mean arterial pressure (MAP)], oxidative stress, and PRA in the presence or absence of chronic NO synthase inhibition. SHR were divided into four groups: control, Tempol (1 mmol/l) alone, nitro-L-arginine methyl ester (L-NAME, 4.5 mg·kg -1·day-1) alone, and Tempol + L-NAME for 2 wk. With Tempol, MAP decreased by 22%: 191 ± 3 and 162 ± 21 mmHg for control and Tempol, respectively (P < 0.05). L-NAME increased MAP by 16% (222 ± 2 mmHg, P < 0.01), and L-NAME + Tempol abolished the depressor response to Tempol (215 ± 3 mmHg, P < 0.01). PRA was not affected by Tempol but was increased slightly with L-NAME alone and 4.4-fold with L-NAME + Tempol. Urinary nitrate/nitrite increased with Tempol and decreased with L-NAME and L-NAME + Tempol. Tempol significantly reduced oxidative stress in the presence and absence of L-NAME. In conclusion, in SHR, Tempol administration for 2 wk reduces oxidative stress in the presence or absence of NO. but in the absence of NO, Tempol is unable to reduce MAP. Therefore, NO, but not changes in PRA. plays a major role in the blood pressure-lowering effects of Tempol. These data suggest that, in hypertensive individuals with endothelial damage and chronic NO deficiency, antioxidants may be able to reduce oxidative stress but not blood pressure.
AB - The roles of nitric oxide (NO) and plasma renin activity (PRA) in the depressor response to chronic administration of Tempol in spontaneously hypertensive rats (SHR) are not clear. The present study was done to determine the effect of 2 wk of Tempol treatment on blood pressure [mean arterial pressure (MAP)], oxidative stress, and PRA in the presence or absence of chronic NO synthase inhibition. SHR were divided into four groups: control, Tempol (1 mmol/l) alone, nitro-L-arginine methyl ester (L-NAME, 4.5 mg·kg -1·day-1) alone, and Tempol + L-NAME for 2 wk. With Tempol, MAP decreased by 22%: 191 ± 3 and 162 ± 21 mmHg for control and Tempol, respectively (P < 0.05). L-NAME increased MAP by 16% (222 ± 2 mmHg, P < 0.01), and L-NAME + Tempol abolished the depressor response to Tempol (215 ± 3 mmHg, P < 0.01). PRA was not affected by Tempol but was increased slightly with L-NAME alone and 4.4-fold with L-NAME + Tempol. Urinary nitrate/nitrite increased with Tempol and decreased with L-NAME and L-NAME + Tempol. Tempol significantly reduced oxidative stress in the presence and absence of L-NAME. In conclusion, in SHR, Tempol administration for 2 wk reduces oxidative stress in the presence or absence of NO. but in the absence of NO, Tempol is unable to reduce MAP. Therefore, NO, but not changes in PRA. plays a major role in the blood pressure-lowering effects of Tempol. These data suggest that, in hypertensive individuals with endothelial damage and chronic NO deficiency, antioxidants may be able to reduce oxidative stress but not blood pressure.
KW - Antioxidant
KW - Nitric oxide
KW - Renin-angiotensin system
KW - Superoxide
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U2 - 10.1152/ajpregu.00530.2004
DO - 10.1152/ajpregu.00530.2004
M3 - Article
C2 - 15604302
AN - SCOPUS:15544370549
VL - 288
SP - R903-R908
JO - American Journal of Physiology
JF - American Journal of Physiology
SN - 0363-6119
IS - 4 57-4
ER -