Manning R D, Meng S, Tian N
Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS 39216, USA.
Acta Physiol Scand. 2003 Nov;179(3):243-50. doi: 10.1046/j.0001-6772.2003.01204.x.
Oxidative stress occurs in a tissue or in the whole body when the total oxidant production exceeds the antioxidant capacity. Recent studies in human essential hypertension indicate that free radical production is increased and antioxidant levels are decreased, and more than one-half of these hypertensives have a salt-sensitive type of hypertension with progressive renal damage. Increased oxidative stress may also play a critical role in animal models of salt-sensitive hypertension. The stroke-prone spontaneously hypertensive rats (SHRSP) exhibits salt-sensitivity, vascular release of superoxide is increased, and total plasma antioxidant capacity is decreased. The superoxide release in the SHRSP rats inactivates nitric oxide, and superoxide dismutase (SOD) administration returns the bioactive nitric oxide levels to normal. The deoxycorticosterone acetate (DOCA)-salt hypertensive rat is salt-sensitive, aortic superoxide production is increased, and renal inflammation is significant. Treatment of the DOCA-salt rats with apocynin, an NADPH oxidase inhibitor, decreased aortic superoxide production and decreased arterial pressure. The Dahl salt-sensitive (S) rat has increased mesenteric microvascular and renal superoxide production and increased plasma levels of H2O2. The renal protein expression of SOD is decreased in the kidney of Dahl S rats, and long-term administration of Tempol, a superoxide mimetic, significantly decreased arterial pressure and renal damage. In conclusion, both human hypertension and experimental models of salt-sensitive hypertension have increased superoxide release, decreased antioxidant capacity and elevated renal damage.
当总氧化剂生成量超过抗氧化能力时，氧化应激会在组织或全身发生。近期对人类原发性高血压的研究表明，自由基生成增加而抗氧化剂水平降低，并且超过一半的高血压患者患有盐敏感性高血压类型并伴有进行性肾损伤。氧化应激增加在盐敏感性高血压动物模型中也可能起关键作用。易发生中风的自发性高血压大鼠（SHRSP）表现出盐敏感性，超氧化物的血管释放增加，而血浆总抗氧化能力降低。SHRSP大鼠中的超氧化物释放使一氧化氮失活，给予超氧化物歧化酶（SOD）可使生物活性一氧化氮水平恢复正常。醋酸脱氧皮质酮（DOCA）-盐高血压大鼠具有盐敏感性，主动脉中超氧化物生成增加，且肾脏炎症明显。用NADPH氧化酶抑制剂阿朴吗啡治疗DOCA-盐大鼠，可降低主动脉中超氧化物生成并降低动脉血压。Dahl盐敏感（S）大鼠的肠系膜微血管和肾脏中超氧化物生成增加，血浆H2O2水平升高。Dahl S大鼠肾脏中SOD的蛋白表达降低，长期给予超氧化物模拟物Tempol可显著降低动脉血压和肾损伤。总之，人类高血压和盐敏感性高血压实验模型均存在超氧化物释放增加、抗氧化能力降低以及肾损伤加重的情况。
