Thick ascending limbs (THALs) absorb 25% of the filtered NaCl. Endothelin‐1 (ET‐1) inhibits NaCl absorption in THALs by increasing NO and reducing Na/K/2Cl cotransporter (NKCC2) activity via ETB receptors. THAL NaCl absorption is enhanced while NO production is reduced in angiotensin II (Ang II)‐hypertensive rats. Thus, we hypothesized that inhibition of NKCC2 by ET‐1 is blunted in Ang II‐induced hypertension. Rats were infused with vehicle or Ang II 200 ng/kg/min. At day 5 we measured: 1) mean arterial blood pressure (MABP) in anesthetized rats; 2) NKCC2 activity in perfused THALs by fluorescence microscopy and; 3) NOS3 and ETB receptor expression in THALs by Western blot. Ang II infusion increased MABP from 84 ± 5 mmHg to 98 ± 1 mmHg (p< 0.01). In vehicle‐treated rats, 1 nM ET‐1 reduced NKCC2 activity from 1.65 ± 0.15 to 0.84 ± 0.14 AU/s (Δ= ‐50 ± 7 %, p<0.01). In contrast, in Ang II‐hypertensive rats, ET‐1 did not decrease NKCC2 activity (from 1.46 ± 0.24 to 1.21 ± 0.22 AU/s). Ang II treatment reduced NOS3 expression by 35 ± 13% (p<0.03) but did not decrease ETB receptor expression (Δ= 10 ± 10%). We conclude that inhibition of NKCC2 activity by ET‐1 is blunted in Ang II‐induced hypertension and this is likely due to a reduction in NOS3 expression rather than ETB receptors. Impaired ET‐1‐induced inhibition of NKCC2 activity could be the cause of the enhanced NaCl absorption seen in this model of hypertension.Sources of funding: NIH HL 028982 to J.L.G. and AHA 11PRE7510005 to V.D.R