Abstract
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.
Published Version
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