on November 10, 2008
Published online before print November 10, 2008, doi: 10.1161/HYPERTENSIONAHA.108.120212
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Submitted on July 21, 2008
From the Division of Hypertension and Vascular Research (G.B.S., J.L.G.), Henry Ford Hospital, Detroit, Mich; and the Department of Physiology (J.L.G.), School of Medicine, Wayne State University, Detroit, Mich. * To whom correspondence should be addressed. E-mail: jgarvin1{at}hfhs.org.
Abstract—Renal medullary superoxide (O2-) increases in angiotensin (Ang) II–dependent hypertension. O2- 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 O2- production and increased protein kinase C (PKC)
Revised on August 8, 2008
Angiotensin II–Dependent Hypertension Increases Na Transport-Related Oxygen Consumption by the Thick Ascending Limb
Guillermo B. Silva and Jeffrey L. Garvin*
activity. We measured the effect of Ang II–dependent hypertension on furosemide-sensitive oxygen consumption (a measure of Na transport), O2- production, and PKC translocation (a measure of PKC 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). O2- was also increased (1.1±0.2 versus 3.2±0.5 nmol of O2-/min per milligram of protein; P<0.03) in thick ascending limbs. Unilateral renal infusion of Tempol decreased O2- (2.4±0.4 versus 1.2±0.2 nmol of O2-/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 O2- or furosemide-sensitive oxygen consumption in normotensive controls and did not alter systolic blood pressure. Ang II–dependent hypertension increased PKC 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 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 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 O2- and PKC activity.
Key words: ion transport • reactive oxygen species • kidney • Na/K/2Cl cotransporter
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