Superoxide (O2) is a free radical that contributes to the development of high blood pressure. During angiotensin (Ang) II– dependent hypertension there is an increased O2 production in the cardiovascular system, central nervous system, and kidney. Elevated oxidative stress in the kidney may contribute to the development and maintenance of Ang II– dependent hypertension. Enhanced O2 production in the renal medulla increases blood pressure, and renal O2 scavenging decreases blood pressure in several models of hypertension.
Augmented O2 production in the kidney increases blood pressure by promoting Na retention. O2-induced Na retention may occur as a result of decreased glomerular filtration rate and renal blood flow. However, O2 may also decrease urinary volume and urinary Na excretion without changing renal blood flow and glomerular filtration rate. Such data indicate that O2 has a direct effect on tubular transport. The thick ascending limb reabsorbs 25% to 30% of the total filtered NaCl load. Increases in Na transport by this segment contribute to several forms of hypertension, and diuretics that decrease thick ascending limb NaCl absorption are frequently used to reduce blood pressure. Acute increases in exogenous O2 in the thick ascending limb enhance Na transport, whereas scavenging endogenous O2 decreases it. We have shown previously that O2 stimulates NaCl reabsorption by activating protein kinase C (PKC).
Ang II acutely enhances NaCl reabsorption in the thick ascending limb, whereas blockade of Ang II receptors decreases it. Brief exposure of thick ascending limbs to Ang II also results in augmented O2 production. Thus, it is likely that at least part of the acute effect of Ang II on the thick ascending limb is because of O2. However, the chronic effects of Ang II–induced hypertension on NaCl absorption in this segment and the role of O2 have not been studied. We hypothesize that Ang II– dependent hypertension increases Na transport–related oxygen consumption by thick ascending limbs because of enhanced O2 production and the resulting PKC activation.
Augmented O2 production in the kidney increases blood pressure by promoting Na retention. O2-induced Na retention may occur as a result of decreased glomerular filtration rate and renal blood flow. However, O2 may also decrease urinary volume and urinary Na excretion without changing renal blood flow and glomerular filtration rate. Such data indicate that O2 has a direct effect on tubular transport. The thick ascending limb reabsorbs 25% to 30% of the total filtered NaCl load. Increases in Na transport by this segment contribute to several forms of hypertension, and diuretics that decrease thick ascending limb NaCl absorption are frequently used to reduce blood pressure. Acute increases in exogenous O2 in the thick ascending limb enhance Na transport, whereas scavenging endogenous O2 decreases it. We have shown previously that O2 stimulates NaCl reabsorption by activating protein kinase C (PKC).
Ang II acutely enhances NaCl reabsorption in the thick ascending limb, whereas blockade of Ang II receptors decreases it. Brief exposure of thick ascending limbs to Ang II also results in augmented O2 production. Thus, it is likely that at least part of the acute effect of Ang II on the thick ascending limb is because of O2. However, the chronic effects of Ang II–induced hypertension on NaCl absorption in this segment and the role of O2 have not been studied. We hypothesize that Ang II– dependent hypertension increases Na transport–related oxygen consumption by thick ascending limbs because of enhanced O2 production and the resulting PKC activation.
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