Effects of potassium supplementation and deficiency on the progression of salt-sensitive hypertension

Abstract

While the physiological effects of sodium on blood pressure are well established, many of the effects of potassium remain unclear. Prior work found that increased potassium intake decreases blood pressure and risk of cardiovascular disease, improves vasodilation, has reno-protective effects, and can stimulate natriuresis. In this study, we examined how different sodium/potassium ratios affect the development of salt-sensitive hypertension, specifically examining changes in the kidney and the renin angiotensin aldosterone system (RAAS). We hypothesized that blood pressure would directly correlate to the Na+/K+ ratio and that there would be compensatory changes in RAAS and in expression of renal potassium channels, particularly inwardly rectifying potassium (Kir) channels. At 9 weeks of age, male and female Dahl SS rats were placed on a high salt (4% NaCl) diet for 5 weeks with normal potassium (NK, 0.36% K+), high potassium (HK, 1.41% K+), or potassium depleted (DK, <0.0001% K+) diet. After 5 weeks of dietary intervention, DK animals were hypokalemic, and HK animals had significantly increased plasma potassium. Potassium supplementation attenuated the development of salt-sensitive hypertension in male rats fed the HK diet compared to NK; the DK group did not develop hypertension. Potassium supplementation did not attenuate blood pressure in female rats, who also had a higher mortality rate on the DK diet. Heart rates were unchanged in both male and female HK groups but were significantly lower in the DK groups of both sexes. After 5 weeks of diet, the total body weights of DK rats were significantly lower. The 2 kidney/total body weight ratios were not different between the HK and NK groups, but the kidneys of the DK group were significantly larger, likely due to their smaller body weights. Medullary protein casts in DK rats of both sexes were decreased but no renoprotective effects were observed in the HK group. Western blot analysis of renal potassium channels demonstrated no changes in the expression of ROMK, significantly increased Kir5.1 in DK males and females, and a significant increase in Kir4.1 and the alpha-subunit of the Na+/K+-ATPase in DK males. We analyzed RAAS metabolites from plasma samples collected at the endpoint: Ang I (1-10), Ang IV (3-8), and Ang (1-5) were significantly decreased in DK males and females, Ang II (1-8) and Ang III (2-8) were significantly reduced in DK males, and aldosterone was significantly increased in HK males and females. These results provide a comprehensive assessment of how various potassium diets affect the development of salt-sensitive hypertension in both males and females, which will provide a solid foundation for future mechanistic studies. R01DK129227, I01 BX004024, R35HL135749. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.