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 a 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-wk-old male and female SHR using semiquantitative 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 versus SD. In addition, sex differences in transporter abundance are smaller in hypertensive SHR compared with 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, whereas proximal sodium transporter patterns are comparable with 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.NEW & NOTEWORTHY Hypertension comes in many varieties, instigated by unrelated factors including genetic, hormonal, stress, and environmental factors. Hypertension provides a natriuretic stimulus to match sodium output to intake, which controls circulating volume. This study compares two distinct hypertension models and two sexes: SHR (slowly developing genetic HTN) and AngII infusion hypertension. Results define which sodium transporters' activation drives the hypertension versus which transporters' activity is depressed by the hypertension to maintain fluid and electrolyte balance.