The results indicate an Ang II-induced NO release in Af of mice, which is mediated by AT1-R. Thus, Ang II balances its own constrictor action in Af. This control mechanism is very important in view of high renin and angiotensin II concentration in the juxtaglomerular apparatus.

Abstract-Oxidative stress is associated with vascular remodeling and increased preglomerular resistance that are both implicated in the pathogenesis of renal and cardiovascular disease. Angiotensin II induces superoxide production, which is metabolized by superoxide dismutase (SOD) or scavenged by NO. We investigated the hypothesis that SOD1 regulates renal microvascular remodeling, blood pressure, and arteriolar responsiveness and sensitivity to angiotensin II using SOD1-transgenic (SOD1-tg) and SOD1-knockout (SOD1-ko) mice. Blood pressure, measured telemetrically, rose more abruptly during prolonged angiotensin II infusion in SOD1-ko mice. The afferent arteriole media:lumen ratios were reduced in SOD1-tg and increased in SOD1-ko mice. Afferent arterioles from nontreated wild types had graded contraction to angiotensin II (sensitivity: 10 Ϫ9 mol/L; responsiveness: 40%). Angiotensin II contractions were less sensitive (10 Ϫ8 mol/L) and responsive (14%) in SOD1-tg but more sensitive (10 Ϫ13 mol/L) and responsive (89%) in SOD1-ko mice. Arterioles from SOD1-ko had 4-fold increased superoxide formation with angiotensin II at 10 Ϫ9 mol/L. N G -nitro-L-arginine methyl ester reduced arteriole diameter of SOD1-tg and enhanced angiotensin II sensitivity and responsiveness of wild-type and SOD1-tg mice to the level of SOD1-ko mice. SOD mimetic treatment with Tempol increased arteriole diameter and normalized the enhanced sensitivity and responsiveness to angiotensin II of SOD1-ko mice but did not affect wild-type or SOD1-tg mice. Neither SOD1 deficiency nor overexpression was associated with changes in nitrate/nitrite excretion or renal mRNA expression of NO synthase, NADPH oxidase, or SOD2/SOD3 isoforms and angiotensin II receptors. In conclusion, SOD1 limits afferent arteriole remodeling and reduces sensitivity and responsiveness to angiotensin II by reducing superoxide and maintaining NO bioavailability. This may prevent an early and exaggerated blood pressure response to angiotensin II. (Hypertension. 2010;56:907-913.) Key Words: afferent arterioles Ⅲ CuZnSOD Ⅲ hypertension Ⅲ ICSOD Ⅲ oxidative stress Ⅲ superoxide Ⅲ SOD1 Ⅲ kidney O xidative stress implies a shift in the balance between the production of reactive oxygen species (ROS) and the action of antioxidant systems and has been implicated in the pathogenesis of renal and cardiovascular disease. 1,2 NADPH oxidase is an important source of superoxide (O 2 Ϫ ) in the vasculature. O 2 Ϫ that escapes metabolism by superoxide dismutase (SOD) can inactivate NO, 3 and growing evidence demonstrates that oxidative stress and NO deficiency in the kidney contribute to vascular dysfunction and hypertension. 3 Furthermore, a potential crosstalk between NADPH oxidase and SOD activities has been suggested. 4,5 SOD exists as 3 different isoforms: copper-zinc SOD (SOD1), predominately located in the cytoplasm; manganese SOD (SOD2) in the mitochondria; and extracellular SOD (SOD3) in the extracellular space. 6 SOD1 accounts for 60% to 80% of SOD activity in the kidneys and also h...

No abstract