Evidence against a circulating ouabain-like transport inhibitor as a cause of increased red cell sodium in essential hypertension.

Red cell sodium and potassium concentrations, and total ouabain-sensitive and ouabain-insensitive first order red constants for sodium efflux, were measured in 15 patients (11 female, 4 male) with essential hypertension (162 +/- 14/99 +/- 7 (s.d. mmHg) and 15 normotensive control subjects (117 +/- 17/64 +/- 10 mmHg) individually matched for age (45.8 +/- 10 versus 45.7 +/- 10 years, respectively, sex, weight (68.6 +/- 16.1 versus 64.7 +/- 11.2 kg) and blood group. To test for possible plasma inhibitors of sodium transport in hypertension, total efflux rate constants were measured in red cells incubated in two plasma samples, from either the same or the complementary (paired) subjects, respectively. Intracellular sodium was significantly increased in patients (11.8 +/- 3.45 versus 8.75 +/- 2.48 mmols/l of red cell water; P = 0.023). Intracellular potassium and total and ouabain-sensitive sodium efflux rate constants, were similar in both groups. Sodium efflux was similar when cells were incubated in the homologous and complementary plasma samples. Ouabain-insensitive rate constants were decreased in the patients (0.16 +/- 0.08 versus 0.20 +/- 0.05 h-1) but the difference was of borderline significance (P = 0.059). These results confirm the presence of abnormal intracellular sodium concentrations and membrane transport in essential hypertension but are not consistent with the suggestion that the abnormalities are due to a circulating sodium transport inhibitor.

Metabolic effects of high dose amiloride and spironolactone: a comparative study in normal subjects.

Amiloride (75 mg daily) and spironolactone (300 mg daily) were given to five normal subjects for 7 days in order to compare metabolic effects at maximal doses. Blood pressure, body weight, Na+ and K+ balance, and plasma concentrations of Na+, K+, active and total renin, angiotensin II, aldosterone, 11-deoxycorticosterone (DOC), 18-hydroxydeoxycorticosterone (18-OH DOC), corticosterone (B), 18-hydroxycorticosterone (18-OH B) and cortisol were measured before and on each day of treatment. Natriuresis and K+ retention were significantly greater with amiloride. Plasma K+ increased from 4.1 +/- 0.2 to 4.9 +/- 0.2 mmol/l (mean +/- s.d.) on amiloride and from 4.0 +/- 0.2 to 4.4 +/- 0.2 mmol/l with spironolactone. Stimulation of renin, angiotensin II, aldosterone and 18-OH B occurred with both drugs but was greater with amiloride in each case. A transient decrease in systolic and diastolic blood pressure was observed after 2 days of spironolactone treatment but not with amiloride. The slope of the regression of aldosterone on angiotensin II during spironolactone treatment was less than that with amiloride, consistent with partial blockade of aldosterone synthesis by spironolactone. These data suggest that the maximum metabolic effects of amiloride exceed those of spironolactone.

Long-term effects of captopril (SQ14 225) on blood-pressure and hormone levels in essential hypertension.

Captopril, an orally active angiotensin-converting enzyme (ACE) inhibitor, was effective in the long-term reduction of blood-pressure in 17 patients with essential hypertension. The addition of hydrochlorothiazide produced a further hypotensive effect, and the combined treatment produced satisfactory control of the blood-pressure for eight months. Captopril prevented and reversed the secondary hyperaldosteronism and hypokalaemia induced by simultaneous diuretic administration, thus eliminating the need for potassium supplements. The fall in plasma-angiotensin-II and urinary aldosterone and rise in angiotensin I and plasma-renin provide biochemical evidence that captopril inhibits ACE in vivo. No change in circulating venous bradykinin levels could be detected. The hypotensive action of captopril is not mediated by changes in blood-bradykinin but may involve inhibition of the renin-angiotensin and kallikrein-kinin systems locally within the kidneys or blood vessels.