INTRODUCTION AND AIMS: Increased potassium intake has been proved to lower human blood pressure in numerous studies but the mechanisms underlying the role of potassium in human blood pressure regulation are not fully understood. To elucidate this further we performed a potassium supplementation study in healthy normotensive men. The effects of potassium supplementation on plasma vasoactive hormones and 24-hour ambulatory blood pressure were explored. In addition the effect of potassium on endothelial function was assessed through wire-myograph experiments on subcutaneous resistance arteries isolated from gluteal skin- and fat biopsies surgically removed from the participants. METHODS: This is a randomized clinical placebo-controlled double-blind crossover study in healthy normotensive men. Included participants were randomized to either 4 weeks treatment with potassium supplementation (90 mmol potassium daily) or to 4 weeks treatment with placebo. After the first treatment period, a washout period of 2 weeks was inserted, before crossover and completion of the second treatment period. At the end of both treatment periods a fasting blood sample was taken and the participants performed a 24-hour ambulatory blood pressure measurement. Furthermore a gluteal skin- and fat biopsy was performed at the end of both treatment periods and from these biopsies subcutaneous resistance arteries were isolated and mounted in wire-myographs for experiments. The endothelial function of these arteries was assessed through stimulation of the arteries with acetylcholine and substance P. RESULTS: In total 25 normotensive men completed the study and were included in the analysis. Potassium supplementation resulted in a significant increase in plasma renin concentration [70% (95%CI: 20%, 141%); P-value: 0.0047], plasma angiotensin II [74% (24%, 144%); P-value: 0.0025] and plasma aldosterone [85% (55%, 120%); P-value: <0.0001] compared with placebo. Despite marked activation of the renin-angiotensin-aldosterone system, potassium did not change 24-hour ambulatory blood pressure. In the wire-myograph experiments on subcutaneous resistance arteries, potassium did not affect endothelial function as assessed by acetylcholine and substance P. CONCLUSIONS: In conclusion, potassium strongly activated the renin-angiotensin-aldosterone system without changing blood pressure in normotensive men. In addition, potassium did not improve endothelial function.