Ursachen für den Blutdruckanstieg unter HochkaliumHochsalz-Diät und die Rolle des Anions

Abstract

Earlier research has shown, that a very high intake of potassium can lead to an increase in arterial blood pressure (Vitzthum et al. 2014; Böttcher 2016; Marx 2019). However, the reasons for this remained unclear. In the present work, the role of the epithelial sodium channel ENaC was further investigated, the effects of special potassium diets on cardiac function were investigated using echocardiography, and the question of a possible involvement of the vessels was investigated using a vessel-specific TMEM16A-knockout mouse model. In all experiments, the mice received a special potassium chloride diet (KCl-diet) or a potassium citrate diet (Kcitrate-diet) in combination with a high-salt-diet. Either C57bl6 wild-type mice or Sv126 mice were used, the latter having an inducible, vessel-specific TMEM16A knockout (TMEM16A WT and KO). Consistent with previous findings, the C57bl6 animals in the KCl-and Kcitrate-groups showed an increase in blood pressure on the high-potassium/high-salt diet. The heart rate also significantly increased under diet in the Kcitrate-group. The administration of the ENaC blocker amiloride did not normalize the blood pressure in any group. Echocardiography showed a significant increase in ejection fraction and a significant decrease in end-systolic volume for the KCl-group. No significant effects could be shown in the Kcitrate-group by means of echocardiography. The TMEM16A WT and KO animals showed an increase in blood pressure on a normal-potassium/high-salt diet but no further increase in pressure on a high-potassium/high-salt diet. When switching to the high-potassium/high-salt diet, a significant initial drop in diastolic blood pressure was only observed in the TMEM16A KO animals of the Kcitrate-group. The TMEM16A KO animals of the KCl-group did not show this decrease. From these results it can be concluded that increased activation of the ENaC does not appear to be the cause of the observed rise in blood pressure. The changes in heart rate and ejection fraction indicate increased sympathetic or reduced parasympathetic activity under a high-potassium/high-salt diet and could be an indication of the cause of the rise in blood pressure. Also the anions used - chloride and citrate - seem to have a different influence on blood pressure regulation.