DOCA-salt 및 L-NAME 고혈압 흰쥐에서 Tempol이 혈압과 조직 산화 스트레스에 미치는 영향

배 경 : 산화 스트레스 감약제가 고혈압 발생과 조직의 산화 스트레스 지표에 미치는 영향을 조사하였다.방 법 : Sprague-Dawley 숫쥐에 deoxycorticosterone acetate (DOCA)-salt 또는 NG- nitro-L-arginine methyl ester (L-NAME)를 처치하여 고혈압을 일으킴과 동시에 산화 스트레스 억제제 4-hydroxyl-2,2,6,6-tetramethylpiperidine-1-oxyl (Tempol)를 투여하였다. 4주째 되는 날 신장과 흉부 대동맥을 적출하여 endothelial nitric oxide synthase (eNOS)와 nitrotyrosine 단백 발현을 조사하였다. 결 과 : Tempol에 의해 DOCA-salt 고혈압 발생은 차단되었으나, L-NAME 고혈압은 영향 받지 않았다. DOCA-salt 고혈압에서 신피질의 eNOS 발현은 증가하되 그 정도는 Tempol에 의해 감약되었으며, nitrotyrosine 발현은 감소하되 Tempol에 의해 더욱 심화되었다. 반면 동맥에서 eNOS 및 nitrotyrosine 발현은 모두 감소를 보이며 이는 Tempol에 의해 영향 받지 않았다. L-NAME 고혈압에서 신피질의 eNOS 발현은 증가하나 그 정도는 Tempol에 의해 감약되며, nitrotyrosine 발현은 Tempol에 무관하게 유의한 변화를 보이지 않았다. 동맥에서 eNOS 및 nitrotyrosine은 모두 감소를 보이되 전자는 Tempol에 의해 영향 받지 않으나 후자는 더욱 강화되었다. Background : Effects of oxidative stress on the development of deoxycorticosterone acetate (DOCA)- salt or NG-nitro-L-arginine (L-NAME) hypertension were examined. Methods : Male Sprague-Dawley rats were treated with DOCA (200 mg/kg, subcutaneous)-salt or L-NAME (40 mg/L in daily drinking water) for 4 weeks. To reduce the oxidative stress, 4-hydroxyl- 2,2,6,6-tetramethylpiperidine-1-oxyl (Tempol, 3 mM/ L) was cotreated in drinking water. The expression of endothelial nitric oxide synthase (eNOS) and nitrotyrosine proteins was determined in the renal cortex and thoracic aorta. Results : Tempol prevented the development of DOCA-salt hypertension, whereas it was without effect on L-NAME hypertension. In DOCA-salt hypertension, the eNOS expression in the renal cortex was increased, the degree of which was attenuated by Tempol. The renal expression of nitrotyrosine was decreased, which was further decreased by Tempol. In the aorta, the expression of both eNOS and nitrotyrosine was decreased, which was not further affected by Tempol. In L-NAME hypertension, the renal expression of eNOS was significantly increased, which was blocked by Tempol. The expression of eNOS in the aorta was slightly decreased, and was not further affected by Tempol. The renal expression of nitrotyrosine was not significantly altered. However, its expression was significantly decreased in the aorta, and was further reduced by Tempol. Conclusion : The blockade of oxidative stress may attenuate the development of hypertension and provide tissue protection in DOCA-salt hypertension. The blockade of oxidative stress may also contribute to a tissue protection in L-NAME hypertension. (Korean J Nephrol 2006;25(4):525-531) KCI Cita