Triple therapy of severe hypertension with the long-acting cardioselective (3-blockers atenolol and betaxolol in combination with furosemide and minoxidil were effective and well tolerated by most patients in our study. The drug regimens exerted similar, smooth, sustained antihypertensive effects, as demonstrated by clinical and 24-h ambulatory arterial pressure measurements. Although these regimens were effective and convenient, they were associated with several side effects, the most important of which were edema and cardiac enlargement. The cardiac enlargement was probably due to a preloading effect on the left ventricle from sodium and water retention. It was not likely to be an afterloading effect, since the arterial pressure was significantly decreased with treatment and remained within normal limits during the tripletherapy phase of the study.

Preloading was also the most likely cause of right ventricular enlargement; an increase in pulmonary pressure could have been a factor, but it was not measured. Previous studies also showed that long-term administration of minoxidil is associated with cardiomegaly and pulmonary hypertension. However, most of these studies used cardio-thoracic ratios to estimate cardiac size, and only one used sequential echocardiography in four patients. These authors admitted that their results were preliminary and that larger studies were needed to determine the effects of minoxidil on the heart.
This is the only large-scale study to our knowledge that used sequential echocardiography to estimate ventricular size before and after prolonged administration of minoxidil. Minoxidil is a potent vasodilator, and its administration triggers strong counteregulatory mechanisms, with stimulation of the sympathetic and the renin-angiotensin systems.* The end result of these counteregulatory mechanisms is sodium and water retention, leading to plasma volume expansion and increases in cardiac preload and cardiac output. Also, a recent study2* demonstrated that spontaneously hypertensive rats treated with minoxidil monotherapy developed significant ventricular dilatation, with an increase in end-diastolic pressure. In contrast, these changes were not seen in rats treated with the new calcium channel blocker nisoldipine.