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(Hypertension. 2009;54:120.)
© 2009 American Heart Association, Inc.

Original Articles

Enhanced Distal Nephron Sodium Reabsorption in Chronic Angiotensin II–Infused Mice

From the Department of Physiology and Hypertension and Renal Center of Excellence, Tulane University School of Medicine, New Orleans, La.

Correspondence to Di Zhao, Department of Physiology SL-39, Tulane University Health Sciences Center, 1430 Tulane Ave, New Orleans, LA 70112. E-mail dzhao{at}tulane.edu

Chronic angiotensin II (Ang II) infusions enhance urinary excretion of angiotensinogen, suggesting augmentation of distal nephron sodium reabsorption. To assess whether chronic Ang II infusions (15 ng/min for 2 weeks) enhance distal nephron sodium reabsorption, we compared sodium excretion before and after blockade of the 2 main distal nephron sodium transporters by IV amiloride (5 mg/kg of body weight) plus bendroflumethiazide (12 mg/kg of body weight) in male C57/BL6 anesthetized control mice (n=10) and in chronic Ang II–infused mice (n=8). Chronic Ang II infusions increased systolic blood pressure to 141±6 mm Hg compared with 106±4 mm Hg in control mice. After anesthesia, mean arterial pressure averaged 97±4 mm Hg in chronic Ang II–infused mice compared with 94±3 mm Hg in control mice, allowing comparison of renal function at similar arterial pressures. Ang II–infused mice had lower urinary sodium excretion (0.16±0.04 versus 0.30±0.05 µEq/min; P<0.05), higher distal sodium reabsorption (1.74±0.18 versus 1.12±0.18 µEq/min; P<0.05), and higher fractional reabsorption of distal sodium delivery (91.1±1.8% versus 77.9±4.3%; P<0.05) than control mice. Urinary Ang II concentrations, measured during distal blockade, were greater in Ang II–infused mice (1235.0±277.2 versus 468.9±146.9 fmol/mL; P<0.05). In chronic Ang II–infused mice treated with spironolactone (n=5), fractional reabsorption of distal sodium delivery was similarly augmented as in chronic Ang II–infused mice (94.6±1.7%; P<0.01). These data provide in vivo evidence that there is enhanced distal sodium reabsorption dependent on sodium channel and Na⁺-Cl^– cotransporter activity and increased urinary Ang II concentrations in mice infused chronically with Ang II.

Key Words: tubular sodium reabsorption • filtered sodium • amiloride • bendroflumethiazide • renal plasma flow • glomerular filtration rate