Obesity enhances salt-sensitivity of blood pressure, independent of skin electrolytes, and more in female than in male ZSF1 rats

Obesity and sex influence the salt-sensitivity of blood pressure, but it is unknown whether this also affects tissue electrolyte accumulation. We hypothesized that obese female rats exhibit greater salt-sensitivity of blood pressure with higher nonosmotic sodium accumulation in skin compared with obese male or lean female rats. To investigate this, male and female lean and obese ZSF1 rats received either a deoxycorticosterone acetate (DOCA) pellet plus a high-salt diet (6% NaCl) or a placebo pellet plus normal salt diet at 19 wk of age. Systolic blood pressure (SBP) and 24-h sodium excretion were measured biweekly from 12 to 26 wk. At 26 wk, sodium and potassium content in the skin was measured. SBP was higher in obese than in lean rats within the DOCA + high-salt groups. Lean female rats showed no SBP increase in response to the DOCA + high-salt diet. Analysis of pressure-natriuresis curves confirmed that obesity increased the salt-sensitivity of blood pressure. Furthermore, there was a significant interaction between sex and obesity on salt-sensitivity of blood pressure: lean female rats were completely salt-resistant, whereas obese female rats showed the greatest salt-sensitivity of blood pressure. Similar trends were observed in males, but the effects were less pronounced. Despite differences in salt-sensitivity of blood pressure, there were no differences in skin electrolytes. In conclusion, obesity enhances salt-sensitive hypertension more in female than in male rats, independent of skin electrolytes.<b>NEW & NOTEWORTHY</b> In the presence of obesity, salt-sensitivity of blood pressure was greater in female than in male ZSF1 rats, whereas in the absence of obesity, female rats were salt-resistant. Interestingly, these differences occurred without changes in sodium or potassium accumulation in the skin. These findings highlight that obesity leads to loss of female advantage in salt-sensitive hypertension and call into question the role of nonosmotic sodium storage in salt-sensitivity of blood pressure.