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The successful use of diuretics depends upon a knowledge of their mode of action, their potency, and their side-effects. The four basic groups of diuretics which cover most situations are: (i) the thiazides, (ii) ethacrynic acid or frusemide, (iii) spironolactone or triamterene, (iv) mannitol.

The kidneys form urine by filtering about 180 litres of filtrate daily and by reabsorbing about 99 % of this filtrate in the tubules. The proximal tubules account for the majority of this reabsorption (60 to 70 %), and the loops of Henle, the distal tubules and the collecting ducts for the rest. The ability of the kidney to form concentrated urine depends upon the pumping of sodium out of the ascending limb of the loop of Henle into the medulla, to form an hypertonic interstitium. In the presence of anti-diuretic hormone (ADH), water is reabsorbed from the collecting ducts as they traverse the hypertonic medulla. Dilute urine is formed by the reabsorption of sodium in the ascending limb of the loop of Henle, and by the passage of this dilute filtrate through the impermeable collecting ducts in the absence of ADH. Potassium and hydrogen ions are exchanged for sodium reabsorbed in the distal tubule under the control of aldosterone.

In this randomised, double-blind, crossover trial, the efficacy in hypertension of atenolol and nifedipine as single agents or in combination was compared. 81 patients with mild to moderate essential hypertension (sitting diastolic blood pressure 100–120mm Hg, aged 20–70 years) from 6 outpatient clinics entered the study. By use of a Latin-square design, patients received, in randomised fashion, sustained release nifedipine 20mg twice daily, atenolol 50mg in the morning and then placebo in the evening, or sustained release nifedipine 20mg plus atenolol 50mg in the morning and then placebo in the evening. Each schedule was followed for 4 weeks. All treatments lowered systolic and diastolic blood pressure in the supine and standing positions compared with pretreatment values. The combination regimen significantly reduced supine and standing systolic (p < 0.01 and p < 0.001, respectively) and diastolic (p < 0.001) blood pressure compared with nifedipine alone, and it also significantly reduced supine and standing systolic (p < 0.01 and p < 0.03, respectively) and diastolic (p < 0.01) blood pressure compared with atenolol alone. Heart rate was significantly decreased by atenolol and the combination compared with nifedipine alone. 15 patients withdrew because of side effects: 9 during nifedipine treatment, 2 during atenolol treatment and 4 during combination treatment. Side effects were typical of those associated with nifedipine or atenolol. Flushes and hot sweats, which were frequent with nifedipine, were significantly less (p < 0.001) with atenolol or the combination. For selected patients who do not respond to monotherapy with nifedipine or atenolol, the combination regimen seems an appropriate and useful alternative to β-blocker/diuretic combinations, especially where ischaemic heart disease may co-exist.