Therapeutic response to canrenone of patients with essential hypertension as a function of sodium transport anomalies and ouabain sensitivity of erythrocytes

The presence of Na+ transport abnormalities (decreased affinity of the Na+/K+ pump or the Na+, K+ cotransport for internal Na+, increased Na+:Li+ countertransport, increased Na+ leak), Na+ content, Na+/K+ pump activity and sensitivity to ouabain were investigated in erythrocytes from 13 patients with essential hypertension. According to the presence or absence of Na+ transport abnormalities, the patients were divided into two groups: TrNa(+) (n = 9) and TrNa(-) (n = 4) respectively. Compared with TrNa(-) patients, TrNa(+) patients were characterized by: (i) a higher arterial pressure (131.4 +/- 11.8 vs 110.0 +/- 13.2 mmHg, p less than 0.05), (ii) an increased erythrocyte Na+ content (8.9 +/- 1.0 vs 6.3 +/- 0.8 mmol/l.cells, p less than 0.01) associated with (iii) a decreased rate constant of Na+/K+ pump activity (235 +/- 26 vs 309 +/- 45 h-1, p less than 0.05) and (iv) a higher sensitivity to ouabain (0.76 +/- 0.23 vs 1.12 +/- 0.26 microM, p less than 0.05). Oral administration of canrenone 50 mg per day during 7 weeks decreased mean arterial pressure by 10-30 mmHg in 6 out of the 9 TrNa(+) patients. Conversely, it decreased mean arterial pressure in only one out of the 4 TrNa(-) patients. The hypotensive effect of canrenone in TrNa(+) patients was not associated with normalization of their Na+/K+ pump activity. Canrenone did not modify the sensitivity to ouabain of either the TrNa(+) or the TrNa(-) patients. Before treatment, acute injection of ouabain provoked an inhibition of the erythrocyte Na+/K+ pump, without any change in Na+ content.(ABSTRACT TRUNCATED AT 250 WORDS)