Captopril and hydrochlorothiazide: rationale for their combination.

The results of controlled clinical studies have shown that about 80% of hypertensive patients have a satisfactory blood pressure reduction when treated with a combination of captopril and thiazide diuretics. The high response rate to this treatment can be explained on the basis of the mechanism of action of these drugs. In the long term, diuretics act by reducing peripheral vascular resistance. The mechanism by which they reduce peripheral vascular resistance is the subject of debate, but could be explained on the basis of cellular ionic changes. From our studies, it was observed that thiazides cause a reduction in intracellular Na+ (Nai) and in intra- and extracellular K+ (Ki, Ke). Since in many patients Ke losses are greater than Ki losses, the Ki/Ke ratio (which is directly related to membrane potential and thus to vascular tone) increases. Captopril also reduces Nai, but its effects on Ke and Ki are quite different from those of thiazides. Captopril in fact causes an increase in Ki inducing a net increase in Ki/Ke. This increase can also be observed when captopril is given in combination with thiazides. Therefore the combination of captopril and thiazides has an additive effect on Nai, and increases Ki/Ke in the vast majority of patients. The decrease in Nai probably acts by reducing membrane sensitivity to catecholamines and angiotensin, whereas the increase in Ki/Ke acts by hyperpolarizing vascular smooth muscle membrane. The combination of captopril an thiazides also has favourable metabolic effects.(ABSTRACT TRUNCATED AT 250 WORDS)