Influence of captopril on intracellular ions--a possible mode of action

The effects on intra- and extracellular Na+ and K+ (Nai, Ki; Nae, Ke) of 2 months treatment with captopril or hydrochlorothiazide given alone or in combination were assessed in 47 hypertensive patients. Before therapy, diastolic blood pressure was directly related to Nai and to Nai/Ki and inversely to Ki. The correlation coefficient was even higher when Ki/Ke was considered instead of Ki alone. Treatment with captopril induced a decrease in Nai, no change in Ke and an increase in Ki and Ki/Ke. Hydrochlorothiazide induced a decrease in Nai, in Ke and in Ki but an increase in Ki/Ke. The Nai decrease was maximal in patients receiving the combination of captopril and hydrochlorothiazide. In these subjects Ke was not reduced and Ki was still increased. The percent reduction in diastolic blood pressure induced by captopril was significantly related to the percent increase in Ki/Ke whereas the reduction induced by hydrochlorothiazide was best related to the decrease in Nai/Nae. These data suggest that blood pressure is related to the Ki/Ke ratio and that any increase in this ratio could produce a fall in blood pressure. This phenomenon can be explained by the Ki/Ke ratio being an important factor in determining membrane potential and thus arterial smooth muscle tone.