Ketanserin, an antagonist of 5-HT2-serotonergic and alpha 1-adrenergic receptors, has come into use for the therapy of mild to moderate arterial hypertension. Quite recent observations have shown changes in transmembrane sodium (Na) transport after the acute administration of high doses of this drug to normal subjects. It is well known that some of these transport systems have an altered activity in essential hypertension. We evaluated the effects of long-term (3 months) administration of ketanserin (40-80 mg/day) on Na and potassium (K) intracellular concentrations and transmembrane fluxes in red blood cells (RBCs) from 12 essential hypertensive patients. In addition the present study describes the in vitro effects of two different concentrations of the drug (5 x 10(-8) and 5 x 10(-7) M) on erythrocytes in normal subjects. In the first study, both systolic and diastolic blood pressure were significantly lowered by the treatment with ketanserin (from 165/103 to 143/89; p less than 0.001). Na and K intraerythrocyte concentrations fell markedly during ketanserin administration (both p less than 0.001). A marked decrease in Na,K-pump activity (p less than 0.001) and an increase in Na,lithium(Li)-countertransport function (p less than 0.001) were observed. Na outward cotransport, Na leak, and K leak were not modified by the therapy. Direct correlation was found between the fall in mean blood pressure and in Na and K intraerythrocyte concentration (respectively, p less than 0.01 and p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)