Summary:Eighteen patients aged 35-70 years (meanf SEM 58 f2) with poorly controlled hypertension on various regimens, participated in the present studies. After a 4-week placebo-controlled lead-in period, 12 patients were randomized to terazosin treatment and 6 to placebo. They were followed in the clinic every 2 weeks for 13 weeks, where their supine (5 min) and the upright (2 min) arterial pressure and heart rate were measured. In addition, all patients had a complete laboratory evaluation at the beginning and end of the study. Depending on pressure response, the experimental drug was increased at each visit from 1 .O mg/day to 2.0,5.0, 15.0, and 20.0 mg/day, if the supine diastolic pressure was gmter than 90 d g .Terazosin decreased the systolic and diastolic pressure in both the supine and upright positions, and had no significant effect on heart rate. Placebo did not exert any effects on either arterial pressure or heart rate. No adverse clini- cal or metabolic effects were observed with the administration of either terazosin or placebo. We conclude that: (1) Terazosin is a new effective long-acting alpha blocker given in combination with other antihypertensive drugs, and (2) it is safe and well tolerated by the patients.

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We investigated the role of adenosine receptors in amitriptyline-induced cardiac action potential (AP) changes in isolated rat atria. In the first group, APs were recorded after cumulative addition of amitriptyline (1 μM, 10 μM and 50 μM). In other groups, each atrium was incubated with selective adenosine A(1) antagonist (8-cyclopentyl-1,3-dipropylxanthine (DPCPX), 10(-4) M) or selective adenosine A(2a) receptor antagonist (8-(3-chlorostyryl) caffeine, 10(-5) M) before amitriptyline administration. Resting membrane potential, AP amplitude (APA), AP duration at 50% and 80% of repolarization (APD(50) and APD(80), respectively), and the maximum rise and decay slopes of AP were recorded. Amitriptyline (50 μM) prolonged the APD(50) and APD(80) (p < 0.001) and the maximum rise slope of AP was reduced by amitriptyline (p < 0.0001). Amitriptyline reduced maximum decay slope of AP only at 50 μM (p < 0.01). DPCPX significantly decreased the 50-μM amitriptyline-induced APD(50) and APD(80) prolongation (p < 0.001). DPCPX significantly prevented the effects of amitriptyline (1 μM and 50 μM) on maximum rise slope of AP (p < 0.05). DPCPX significantly prevented the amitriptyline-induced (50 μM) reduction in maximum decay slope of AP (p < 0.001). The selective adenosine A(1) receptor antagonist prevented the electrophysiological effects of amitriptyline on atrial AP. A(1) receptor stimulation may be responsible for the cardiovascular toxic effects produced by amitriptyline.

Summary: Placebo and enalapril were added on a double-blind basis to conventional treatment in 14 patients with congestive heart failure (CHF), New York Heart Association class 11-111. The patients were followed for 14 weeks and their performance was evaluated by a treadmill test, ejection fraction by nuclear scan, cardiothoracic ratio, and Yale Scale score. Metabolic studies were done to test any adverse effects of the drugs. Enalapril decreased arterial pressure and cardiothoracic ratio, and increased ejection fraction. Placebo exerted no significant effects. However, both drugs improved treadmill time and Yale Scale score. No adverse metabolic or clinical effects were observed with either drug. Based on these limited observations we conclude that: ( 1 ) Enalapril is a useful ancillary agent to conventional treatment of CHF; (2) it exerts its effects through afterload and preload reduction; and (3) it is safe and well tolerated and has a prolonged duration of action.