Angiotensin II-Dependent Hypertension Increases Na Transport-Related Oxygen Consumption by the Thick Ascending Limb

Renal medullary superoxide (O-2(-)) increases in angiotensin (Ang) II-dependent hypertension. O-2(-) increases Renal medullary superoxide (O-2(-)) increases in angiotensin (Ang) II-dependent hypertension. O-2(-) increases Renal medullary superoxide (O-2(-)) increases in angiotensin (Ang) II-dependent hypertension. O-2(-) increases thick ascending limb Na transport, but the effect of Ang II-dependent hypertension on the thick ascending limb is unknown. We hypothesized that Ang II-dependent hypertension increases thick ascending limb NaCl transport because of enhanced O-2(-) production and increased protein kinase C (PKC) alpha activity. We measured the effect of Ang II-dependent hypertension on furosemide-sensitive oxygen consumption (a measure of Na transport), O-2(-) production, and PKC alpha translocation (a measure of PKC alpha activity) in thick ascending limb suspensions. Ang II-dependent hypertension increased furosemide-sensitive oxygen consumption (26.2 +/- 1.0% versus 36.6 +/- 1.2% of total oxygen consumption; P < 0.01). O-2(-) was also increased (1.1 +/- 0.2 versus 3.2 +/- 0.5 nmol of O-2(-)/min per milligram of protein; P < 0.03) in thick ascending limbs. Unilateral renal infusion of Tempol decreased O-2(-) (2.4 +/- 0.4 versus 1.2 +/- 0.2 nmol of O-2(-)/min per milligram of protein; P < 0.04) and furosemide-sensitive oxygen consumption (32.8 +/- 1.3% versus 24.0 +/- 2.1% of total oxygen consumption; P < 0.01) in hypertensive rats. Tempol did not affect O-2(-) or furosemide-sensitive oxygen consumption in normotensive controls and did not alter systolic blood pressure. Ang II-dependent hypertension increased PKC alpha translocation (5.7 +/- 0.3 versus 13.8 +/- 1.4 AU per milligram of protein; P < 0.01). Unilateral renal infusion of Tempol reduced PKC alpha translocation (5.0 +/- 0.9 versus 10.4 +/- 2.6 AU per milligram of protein; P < 0.04) in hypertensive rats. Unilateral renal infusion of the PKC alpha inhibitor Go6976 reduced furosemide-sensitive oxygen consumption (37.4 +/- 1.5% versus 25.1 +/- 1.0% of total oxygen consumption; P < 0.01) in hypertensive rats. We conclude that Ang II-dependent hypertension enhances thick ascending limb Na transport-related oxygen consumption by increasing O-2(-) and PKC alpha activity. (Hypertension. 2008; 52: 1091-1098.)