Potassium supplementation and depletion during development of salt-sensitive hypertension in male and female SS rats

The dietary sodium/potassium ratio is positively correlated with blood pressure, and understanding this relationship is crucial for improving hypertension treatment. Moreover, few studies have examined these effects in both sexes. In this study, we aimed to investigate how supplementing (1.41% K+; HK) or depleting (DK) dietary potassium affects the development of salt-sensitive (SS) hypertension in male and female Dahl SS rats. Potassium supplementation attenuated blood pressure during 5 weeks of high-salt (4% NaCl) diet in male but not in female rats. In contrast, a potassium-deficient diet prevented the development of salt-induced hypertension in both sexes, though this effect is unlikely to be protective. Both males and females on the DK diet were hypokalemic and had diminished heart rates and reduced weight gain; furthermore, females experienced high mortality. RNA-Seq of kidney cortical tissue revealed a number of genes that may underlie the sex-specific differences in phenotype. Male rats supplemented with potassium exhibited a decreased number and size of WNK4 puncta, whereas in potassium-supplemented females, there was no difference in puncta count and there was an increase in puncta size. Our data indicate there are sex-dependent differences in response to dietary potassium in hypertension and that the distal nephron compensates for severe potassium deficiency.