Angiotensin II-dependent hypertension increases Na transport-related oxygen consumption by the thick ascending limb.

Guillermo B Silva, Jeffrey L Garvin

Index: Hypertension 52(6) , 1091-8, (2008)

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Abstract

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 PKCalpha translocation (a measure of PKCalpha 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 PKCalpha translocation (5.7+/-0.3 versus 13.8+/-1.4 AU per milligram of protein; P<0.01). Unilateral renal infusion of Tempol reduced PKCalpha 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 PKCalpha inhibitor Gö6976 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 PKCalpha activity.