NOS1‐specific activity is lost and NOS3‐specific activity is attenuated in the renal inner medulla of male spontaneously hypertensive rats (SHR) compared to female SHR.

We have previously shown that male SHR have higher levels of renal inner medullary oxidative stress and greater Na+ reabsorption compared to female SHR. Nitric oxide (NO) contributes to the regulation of water and Na+ excretion and the inner medulla contains the greatest NOS protein and activity in the kidney. Therefore, we hypothesized that female SHR have greater NOS activity/expression in the renal inner medulla. 14‐week old male (177±6 mmHg) and female (160±2 mmHg) SHR were studied. Total NOS activity was less in inner medullary homogenates from male SHR compared to females (pmol/mg: 57±9 vs. 201±40, p=0.005). NOS‐isoform specific activity was determined using isoform‐specific inhibitors and male SHR had less NOS1 (pmol/mg: 0.3±3 vs. 31±19, p=0.04) and NOS3 (pmol/mg: 53±7 vs. 189±41, p=0.01) specific activities in the inner medulla compared to females. There was no detectable NOS2 activity. NOS1 protein expression was also lower in the inner medulla of male SHR (RDU: 24±4 vs. 50±11, p=0.05). Total NOS3 protein expression was comparable in the inner medulla of male and female SHR, however, there was greater NOS3 phosphorylated on threonine reside 495 in males (RDU: 0.8±0.01 vs. 0.05±0.01, p=0.05) and phosphorylation on this residue is associated with decreased NO production. Therefore, greater NOS expression/activity in the inner medulla of female SHR may contribute to the maintenance of a lower blood pressure.