Acute hypotensive, natriuretic, and hormonal effects of nifedipine in salt-sensitive and salt-resistant black normotensive and hypertensive subjects.
In a randomized double-blind study, we compared the short-term effects of nifedipine (10 mg 3x daily for 1 day) versus placebo on 24-h blood pressure, diuresis, natriuresis, urinary excretion of dopamine and metabolites, and on plasma renin activity (PRA) and plasma aldosterone levels in 18 black hypertensive (HT) patients [eight salt-resistant (HT-SR) and 10 salt-sensitive (HT-SS)], and in 20 black normotensive (NT) subjects (12 NT-SR and eight NT-SS) who were studied randomly with both a high- (HS) and a low-salt (LS) diet. In comparison to placebo, nifedipine significantly decreased 24-h mean BP in all groups either with HS or LS diets (all p<0.05). With HS, greater hypotensive effects were achieved in NT-SS (-10+/-2 mm Hg) versus NT-SR (-3+/-1 mm Hg; p<0.05) and in HT-SS (-18+/-2 mm Hg) versus HT-SR (-12+/-2 mm Hg; p<0.05). In NT-SS and HT-SS, nifedipine induced greater (p<0.05) BP decrease with HS (-10+/-2 and -18+/-2 mm Hg) than with LS (-4+/-1 and -9+/-1 mm Hg, respectively), whereas in NT-SR and HT-SR, the hypotensive effect did not differ between HS and LS. Nifedipine versus placebo significantly increased natriuresis and fractional excretion of sodium in all groups only with HS (p<0.05) but not with LS diets. Only in HT-SS were the hypotensive and natriuretic effects of nifedipine significantly correlated (r = -0.77; p<0.01). Nifedipine produced a similar increase of the urinary excretion of dopamine, L-DOPA, and of DOPAC in all subjects, which did not correlate with hypotensive and natriuretic effects. Nifedipine did not modify plasma levels of renin and of aldosterone except in NT-SS with HS, in whom nifedipine increased PRA levels (p <0.05). We conclude that although nifedipine reduces BP in all groups of NT and HT with LS and HS diets, the effect is greater in salt-sensitive subjects with HS. Although in HT-SS with HS, the short-term natriuretic response to nifedipine may contribute to its hypotensive effects, the diuretic-natriuretic effect of nifedipine is not necessary for the expression of its hypotensive effect. Moreover, it is unlikely that any short-term effects of nifedipine either on the renal dopaminergic system or on the secretion of aldosterone explain nifedipine short-term hypotensive and diuretic-natriuretic effects.
Damasceno
A
A
Faculdade Medicina Universidade Eduardo Mondlane, Maputo, Mozambique.
Santos
A
A
Pestana
M
M
Serrão
P
P
Caupers
P
P
Soares-da-Silva
P
P
Polónia
J
J
D000328:Adult; D000450:Aldosterone / Q000378:metabolism; D000959:Antihypertensive Agents / Q000494:pharmacology*; D044383:Black People; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D003710:Demography; D004232:Diuretics / Q000494:pharmacology; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000378:metabolism; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D007677:Kidney Function Tests; D008297:Male; D009318:Natriuresis / Q000187:drug effects*; D009543:Nifedipine / Q000627:therapeutic use*; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism; D012083:Renin / Q000378:metabolism; D012965:Sodium Chloride / Q000494:pharmacology*
D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D004232:Diuretics; D011954:Receptors, Dopamine; D012965:Sodium Chloride; D000450:Aldosterone; D012083:Renin; D009543:Nifedipine