Sexual dimorphic pattern of renal transporters and channels in spontaneously hypertensive rats

Male-female differences in the pattern of renal transporters have been reported for normotensive Sprague Dawley (SD) rats at baseline, when fed with high-salt diet, and when infused with angiotensin II which raises blood pressure (AngII-HTN). Whether these sexual dimorphic patterns are evident in spontaneously hypertensive rats (SHR), which exhibit elevated blood pressure from an early age, is unclear. In this study, we profile renal transporters and channels in 14-week-old male and female SHR using semi-quantitative immunoblots, then performed an integrative analysis comparing sexual dimorphisms in renal transporter abundance across conditions. We found that renal transporter profiles exhibit similar patterns of sex differences in hypertensive SHR as reported for normotensive SD, albeit responses are moderated in hypertensive SHR verses SD. Additionally, sex differences in transporter abundance are smaller in hypertensive SHR compared to sex differences in hypertensive AngII-HTN SD rats. In particular, along the distal nephron, male and female SHR exhibit greater abundance and activation of transporters and channels while proximal sodium transporter patterns are comparable to those in normotensive SD. These findings are consistent with previous physiological studies reporting that male SHR have blunted acute pressure-natriuresis responses and higher renin-angiotensin-aldosterone system activity. Moreover, comparison with normotensive SD rats fed high-salt diet suggests that renal transporter profiles in male and female SHR may be more a function of the pressure natriuresis response than salt overload.