Acute angiotensin II infusions elicit pressure natriuresis in mice and reduce distal fractional sodium reabsorption.
Acute angiotensin II (Ang II) infusions into mice increase arterial pressure (AP) and elicit pressure natriuresis. We used this model of pressure natriuresis to delineate the distal nephron responses to AP-mediated increases in distal sodium delivery. In the first group, we measured changes in urinary sodium excretion (U(Na)V) in male C57/BL6 anesthetized mice (n=9) before and during acute Ang II infusions (5 ng/g of body weight per minute). Acute Ang II infusions increased AP (98+/-3 to 126+/-5 mm Hg; P<0.001), urine flow (2.7+/-0.5 to 6.0+/-0.8 microL/min; P<0.01), and U(Na)V (0.6+/-0.2 to 1.3+/-0.2 microEq/min; P<0.05). There were significant relationships between U(Na)V and urine flow (y=0.207x+0.030; P<0.0001) and between U(Na)V and AP (y=0.027x-2.100). In a separate series, distal sodium delivery and fractional reabsorption of distal sodium delivery were determined in control (n=12) and Ang II-infused mice (n=8) by comparing U(Na)V before and after blockade of the 2 major distal nephron sodium transporters with amiloride (5 mg/kg of body weight) plus bendroflumethiazide (12 mg/kg of body weight). A positive relationship was found between U(Na)V (y=0.015x-1.100; P<0.0001) or distal sodium delivery (y=0.027x-0.900; P<0.0001) and AP. An inverse relationship was found between fractional reabsorption of distal sodium delivery and AP (y=-0.511x+128.300; P<0.01). These data indicate that Ang II-mediated pressure natriuresis involves an increase in distal sodium delivery combined with a reduced distal nephron fractional sodium reabsorption, suggesting that increased AP prevents the distal nephron transport mechanisms from accommodating the increased distal delivery.
Zhao
Di
D
Department of Physiology and Hypertension and Renal Center of Excellence, Tulane University School of Medicine, New Orleans, LA 70112, USA.
Navar
L Gabriel
LG
D000042:Absorption; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007261:Infusions, Intra-Arterial; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D009318:Natriuresis / Q000187:drug effects*; D009399:Nephrons / Q000187:drug effects* / Q000378:metabolism; D011312:Pressure; D012964:Sodium / Q000378:metabolism*; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D012964:Sodium