By giving diazoxide intravenously and furosemide orally the diastolic blood pressure was kept under 110 mm Hg and the urinary output over 1 L/day for a 2-week period in 25 hypertensive patients with azotemia. During the first 2 weeks of treatment three patients died. Although the 40% decrease in mean arterial pressure in the remaining patients was associated with immediate improvement in the cardiovascular status, for example, clearing of congestive heart failure and papilledema, there was a 19% average increase in BUN and 17% average increase in serum creatinine values. Three months later, however, maintenance of the reduced arterial pressure was associated with average reductions of 24 mg/1100 ml in BUN and of 2.8 mg/100 ml in serum creatinine below control values. Each of the patients who remained on therapy continued to do well. Twenty-six months later six additional patients had died. In the remaining 16 patients the average mean arterial pressure was 117 mm Hg; papilledema had cleared; the average concentration of BUN was 22 mg/100 ml; the average serum creatinine was 1.8 mg/ 100 ml.

The antihypertensive properties of single doses of furosemide were evaluated in 113 patients. Doses over 120 mg consistently produced a fall in arterial pressure whereas smaller doses did not. Thus 20 of 22 patients (90%) who received more than 120 mg had a 26 + 6% average reduction in mean arterial pressure. The hypotensive action began in 30 to 45 minutes, the nadir of the decrease occurred between 2 and 2X hours, and the hypotension usually lasted 10 to 12 hours. Repeated weekly doses of furosemide over a 2-month period in six patients were not associated with development of drug resistance. The antihypertensive properties of doses of furosemide of more than 120 mg seemed to be of about the same potency as ethacrynic acid. The antihypertensive effect of high doses of furosemide did not seem to be related to the diuretic effect or to the decrease in plasma volume.These studies have demonstrated that doses of furosemide of more than 120 mg consistently decreased arterial pressure. The usefulness of this agent in the long-term management of hypertension remains to be determined.

The 24-h blood pressure control of bisoprolol, a new beta-selective, beta-blocking agent, was studied in 240 mild to moderate hypertensive patients in this 4-week, randomized, double-blind, placebo-controlled trial. A once-daily dosing schedule was evaluated by comparing bisoprolol's antihypertensive effectivness and safety at 24 h postdose and 3 h postdose, the latter time intended to correspond to peak effectiveness. Results from this trial demonstrated the antihypertensive effectiveness of once-daily bisprolol at doses ranging from 5-20 mg. Mean reductions from baseline diastolic blood pressure, measured 24 h postdose, were 6.3, 8.8, and 10.1 mmHg for patients receiving bisoprolol 5, 10, and 20 mg, respectively, compared with 1.6 mmHg for placebo-treated patients (p < 0.01); mean reductions from baseline systolic blood pressure for the bisoprolol groups were 8.6, 8.6, and 10.9 mmHg, respectively, versus 3.3 mmHg for placebo (p < or = 0.01); and mean reductions from baseline heart rate for the bisoprolol groups were 5.1, 7.1, and 10.2 beats/min, respectively, compared with a 0.9 beats/min increase in heart rate for the placebo group (p < 0.01). The response rates for bisoprolol-treated patients ranged from 47 to 70% compared with 18% for patients on placebo (p < 0.01). Antihypertensive effects were dose-related and sustained over the 24-h dosing interval. Near maximal antihypertensive effects were achieved within 1 week of initiation of therapy with bisoprolol and were sustained over the course of the trial.(ABSTRACT TRUNCATED AT 250 WORDS)

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