Modifications of intra- and extracellular sodium and potassium. A possible mechanism for the antihypertensive action of captopril and hydrochlorothiazide.
Forty-four essential hypertensive patients were studied during placebo and after 2 months of the following treatments: hydrochlorothiazide 25 mg once daily (group 1); captopril 50 mg twice daily (group 2); hydrochlorothiazide + captopril (group 3). Blood pressure, serum sodium and potassium (Nae, Ke) and intralymphocytic sodium and potassium (Nai, Ki) were measured before and after treatment. During placebo, diastolic blood pressure was directly related to Nai (r = -0.84) and inversely related to Ki (r = -0.81). The correlation was even greater when the Ki:Ke ratio was considered instead of Ki alone (r = -0.91). Hydrochlorothiazide reduced Nai, Ke and Ki. Captopril induced a decrease in Nai, an increase in Ki and no change in Nae or Ke. The association of the two drugs caused a reduction in Nae and Nai and an increase in Ki. All three treatments caused an increase in Ki:Ke ratio which was proportional to the decrease in the blood pressure. While the antihypertensive effect of hydrochlorothiazide seems to be more related to Nai:Nae reduction, the effect of captopril seems to be more related to the increase in Ki:Ke ratio. The results of our study suggest that hyperpolarization of arterial smooth muscle cells, induced by a Ki:Ke ratio increase, along with a reduction in Nai:Nae, might play a role in the antihypertensive effect of captopril and hydrochlorothiazide.
Ambrosioni
E
E
Cattedra e Servizio di Farmacologia Clinica, Policlinico S. Orsola, Università di Bologna, Italy.
Costa
F V
FV
Borghi
C
C
Mussi
A
A
Boschi
S
S
D000328:Adult; D000959:Antihypertensive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002216:Captopril / Q000494:pharmacology* / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D006801:Humans; D006852:Hydrochlorothiazide / Q000494:pharmacology* / Q000627:therapeutic use; D006973:Hypertension / Q000188:drug therapy / Q000378:metabolism*; D008875:Middle Aged; D011188:Potassium / Q000097:blood / Q000378:metabolism*; D012964:Sodium / Q000097:blood / Q000378:metabolism*
D000959:Antihypertensive Agents; D006852:Hydrochlorothiazide; D002216:Captopril; D012964:Sodium; D011188:Potassium