Enhanced distal nephron sodium reabsorption in chronic angiotensin II-infused mice.
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 microEq/min; P<0.05), higher distal sodium reabsorption (1.74+/-0.18 versus 1.12+/-0.18 microEq/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.
Zhao
Di
D
Department of Physiology and Hypertension and Renal Center of Excellence, Tulane University School of Medicine, New Orleans, LA 70112, USA. dzhao@tulane.edu
Seth
Dale M
DM
Navar
L Gabriel
LG
D000804:Angiotensin II / Q000008:administration & dosage / Q000494:pharmacology* / Q000652:urine; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007260:Infusion Pumps; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009399:Nephrons / Q000098:blood supply / Q000378:metabolism*; D017595:Renal Plasma Flow / Q000187:drug effects; D012964:Sodium / Q000378:metabolism* / Q000652:urine; D014563:Urodynamics / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000008:administration & dosage / Q000494:pharmacology
D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D012964:Sodium