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Nifedipine, given to both normotensive and hypertensive subjects, caused a greater fall in blood pressure the higher the initial blood pressure. Increasing salt intake enhanced the acute blood-pressure-lowering effect of nifedipine in both normotensive and hypertensive subjects. In hypertensive subjects on longer-term treatment with nifedipine tablets, the addition of bendrofluazide caused no further significant fall in blood pressure. These findings provide circumstantial evidence that there may be a link between sodium intake, sodium balance, and inhibitor of sodium transport, and a functional abnormality of the smooth muscle cell to calcium-entry antagonists.

Twenty-three unselected patients with mild to moderate essential hypertension whose average supine blood pressure after 2 months of observation on no treatment was 154/99 mm Hg were entered into an 8-week double-blind randomised crossover study of 1 month's treatment with slow release potassium tablets (64 mmol/day) versus placebo without alteration of dietary sodium or potassium intake. By the fourth week mean supine blood pressure had fallen by 4% with potassium supplementation compared with placebo. In a separate metabolic study the effect of 12 slow release potassium tablets (98 mmol/day) was studied in 12 patients with mild essential hypertension who had a fixed sodium and potassium intake. The increase in potassium intake caused immediate natriuresis with an average cumulative sodium loss of 110 mmol per patient. In spite of this loss of sodium there was no rise in plasma renin activity, but there was a significant increase in plasma noradrenaline level. On an average western diet containing approximately 150 mmol of sodium/day, potassium chloride supplementation causes a small but worthwhile fall in blood pressure in many patients with essential hypertension. It is likely that part of the mechanism of this fall in blood pressure is related to the increase in potassium intake causing a loss of sodium with no compensatory rise in renin release.

Nifedipine was given to 15 patients with essential hypertension for 6 weeks and to 8 normotensive subjects for 5 days. In the hypertensives, 30 min after the first dose of nifedipine (5-mg capsule), there was a 13.9% fall in mean blood pressure (p less than 0.001), and, at the 6th week of treatment at the maximum dose of 20 mg t.d.s., a 20.6% fall in mean blood pressure (p less than 0.001). In the normotensive subjects, 30 min after the first dose of 5 mg of nifedipine, there was a 2.3% fall in mean blood pressure (NS), and on the 5th day with the maximum dose of 20 mg t.d.s., the fall was 2.2% (NS). In view of the difference in age between these normotensive and hypertensive subjects, a larger group of patients with essential hypertension and older normotensive subjects were also studied acutely after a single 5-mg capsule of nifedipine. Thirty minutes after the first dose of nifedipine in the larger group of hypertensives, there was a significant fall in mean blood pressure (10.4%; p less than 0.001, n = 33). In the normotensive subjects, there was also a significant fall in mean blood pressure (4.7%; p less than 0.01, n = 29). This was significantly less than in the hypertensives (p less than 0.001). In both the normotensive and hypertensive subjects, there was a significant correlation between pretreatment blood pressure and percentage decrease in blood pressure with nifedipine. Nifedipine, therefore, has a greater blood pressure-lowering effect the higher the initial blood pressure. This finding is compatible with the idea that nifedipine reveals a functional abnormality of vascular smooth muscle that becomes greater the higher the blood pressure.