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

• Published in: Hypertension (Dallas, Tex. 1979) Vol. 52; no. 6; pp. 1091 - 1098
• Main Authors: Silva, Guillermo B, Garvin, Jeffrey L
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD American Heart Association, Inc 01.12.2008; Lippincott Williams & Wilkins
• Subjects: Angiotensin II - pharmacology; Animals; Antioxidants - pharmacology; Arterial hypertension. Arterial hypotension; Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Clinical manifestations. Epidemiology. Investigative techniques. Etiology; Cyclic N-Oxides - pharmacology; Furosemide - pharmacology; Hypertension, Renal - chemically induced; Hypertension, Renal - metabolism; Loop of Henle - drug effects; Loop of Henle - metabolism; Male; Medical sciences; Oxygen Consumption - drug effects; Oxygen Consumption - physiology; Protein Kinase C-alpha - metabolism; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species - metabolism; Sodium - metabolism; Sodium Potassium Chloride Symporter Inhibitors - pharmacology; Sodium-Potassium-Chloride Symporters - metabolism; Spin Labels; Vasoconstrictor Agents - pharmacology; Hypertension; Na/K/2Cl cotransporter; kidney; Octapeptide; Oxygen; Peptide hormone; reactive oxygen species; Ion transport; Oxygen consumption; Cardiovascular disease; Angiotensin II
• ISSN: 0194-911X; 1524-4563
• DOI: 10.1161/HYPERTENSIONAHA.108.120212

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) α activity. We measured the effect of Ang II–dependent hypertension on furosemide-sensitive oxygen consumption (a measure of Na transport), O2 production, and PKCα translocation (a measure of PKCα 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 PKCα translocation (5.7±0.3 versus 13.8±1.4 AU per milligram of protein; P<0.01). Unilateral renal infusion of Tempol reduced PKCα 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 PKCα 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 PKCα activity.