The role of antihypertensive drugs in counteracting adverse influence on large arteries.

Studies in humans have shown that chronic elevation of blood pressure induces early alterations in the large arteries, consisting mainly of increased diameter, increased pulse wave velocity, and decreased arterial compliance. Acute reduction of blood pressure, per se, does not necessarily correct these alterations homogeneously. For instance, cadralazine reduced brachial artery diameter and urapidil decreased pulse wave velocity, without accompanying changes in forearm arterial compliance. In contrast, acebutolol, isosorbide dinitrate, nicardipine, and nitrendipine, for the same acute decrease in blood pressure, improved forearm arterial compliance by a concomitant decrease in pulse wave velocity and increase in arterial diameter. To determine whether or not these vascular effects persist with long-term acebutolol therapy, nine hypertensive patients were treated for a period of 3 months. Forearm hemodynamic and cytosolic free calcium concentrations in platelets were simultaneously assessed before and after treatment. Compared with placebo baseline values, chronic acebutolol therapy significantly decreased mean arterial pressure (p less than 0.01), pulse wave velocity (p less than 0.01), and platelet free calcium concentration (p less than 0.05); forearm arterial compliance was increased (p less than 0.01), but brachial artery diameter did not change. Platelet calcium concentration correlated closely with pulse wave velocity even at constant mean arterial pressure. These findings suggest a relaxant effect of acebutolol on the smooth musculature of large arteries, which is independent of changes in blood pressure and arterial diameter, and possibly mediated by changes in cytosolic calcium levels.