SUMMARY The effect on hypertension of hydrochlorothiazide 100 mg daily plus timolol 20-60 mg daily versus hydrochlorothiazide plus placebo and of hydrochlorothiazide plus timolol plus hydralazine 40-200 mg daily versus hydrochlorothiazide plus placebo plus hydralazine was evaluated in a double-blind, randomized, crossover study in 38 patients with hypertension.Hydrochlorothiazide plus timolol was more effective than hydro- chlorothiazide plus placebo in lowering both supine and standing systolic and diastolic blood pressures. Hydrochlorothiazide plus timolol plus hydralazine was a very effective regimen in lowering both supine and standing systolic and diastolic blood pressures. The patients tolerated this regimen well with greater hypotensive activity and a lower incidence of side effects than on hydrochlorothiazide plus placebo plus hydralazine. mm Hg after four weeks of hydrochlorothiazide were excluded from the study. One patient randomized initially to hydrochlorothiazide plus placebo dropped out of the study after two days of hydrochlorothiazide plus placebo because she moved.Thirty-eight men, 33-65 years (mean age 52.4 ± 6.7 years), with a supine diastolic blood pressure > 104 mm Hg after four weeks of hydrochlorothiazide 100 mg daily completed this double-blind, randomized, crossover study. Twenty-three of the 38 subjects were Caucasian, 13 subjects were black, and two subjects were from other racial backgrounds. On a normal salt diet and after two weeks of no medication, five of 38 subjects (13%) had high plasma renin activity, 23 of 38 patients (6 1%) had normal plasma renin activity, and 10 of 38 subjects (26%) had low plasma renin activity.The blood urea nitrogen, serum creatinine, serum potassium, and liver function tests were normal in all patients. None of the patients had coronary heart disease, valvular heart disease, a history of cerebrovascular disease, a history of congestive heart failure, sinus bradycardia, bundle branch block, atrioventricular block, chronic obstructive lung disease, a history of bronchial asthma, allergic rhinitis, peripheral vascular disease, or diabetes mellitus requiring hypoglycemic medication. The patients were maintained on a normal salt diet during the study. Except for potassium chloride, none of the 38 study patients took any medication other than the study medications during this study. Informed consent was obtained from all participants.Supine and upright blood pressures measured with a mercury sphygmomanometer and supine heart rates were recorded on an outpatient basis in all patients, and the results of two blood pressures and heart rates during each visit were averaged in the control period and every two weeks in the 32 weeks on drug treatment. The supine measurements were taken after five minutes of rest in that position, and the upright measurements were taken two minutes after standing.All 38 patients received hydrochlorothiazide 100 mg daily initially for four weeks. During the first treatment period (table 1), 21 patients were randomized in a double-bli...
