Reduced Distal Nephron Sodium Reabsorption in Cyp1a1‐Ren2 Transgenic Rats with Inducible ANG II‐Dependent Malignant Hypertension

Abstract

The present study was performed to determine the ANG II‐dependence of distal nephron sodium reabsorption in Cyp1a1‐Ren2 transgenic rats [strain name: TGR(Cyp1a1‐Ren2)] with inducible ANG II‐dependent malignant hypertension. To assess distal nephron sodium reabsorptive function, we compared sodium excretion before and after blockade of the two main distal nephron sodium transporters by intravenous administration of amiloride (AMIL; 25 μg) plus bendroflumethiazide (BFTZ; 25 μg) in pentobarbital sodium‐anesthetized male Cyp1a1‐Ren2 transgenic rats (n=5). Cyp1a1‐Ren2 transgenic rats induced with 0.3% I3C for 8–10 days exhibited a markedly elevated mean arterial pressure (MAP; 185±5 vs. 131±3 mmHg, P<0.001) compared with non‐induced rats (n=5). Administration of AMIL+BFTZ did not alter MAP in either group, but elicited a greater increase in urinary sodium excretion in the non‐induced control rats than in the hypertensive rats (6.36±1.08 vs. 3.13±0.42 μEq/min, P<0.05). Distal nephron sodium delivery was not different between the two groups (7.43±1.41 vs. 5.24±0.86 μEq/min). However, absolute distal nephron sodium reabsorption and fractional reabsorption of distal nephron sodium delivery were markedly lower in the hypertensive rats than in the normotensive rats (3.13±0.42 vs. 6.36±1.08 μEq/min and 63.37±7.86 vs. 87.97±4.58 %, respectively, P<0.05 in both cases). These findings demonstrate that distal nephron sodium reabsorptive function is markedly decreased in Cyp1a1‐Ren2 rats with ANG II‐dependent malignant hypertension. Such impaired distal nephron sodium reabsorptive function suggests that ANG II‐dependent stimulation of distal nephron sodium reabsorption does not contribute substantively to the hypertension in these rats.