Effects of doxazosin on blood pressure, renin-angiotensin-aldosterone and urinary kallikrein.
Doxazosin, a new quinazoline-derivative postsynaptic alpha 1-adrenoceptor antagonist, was studied in this randomized, double-blind, placebo-controlled 12-week study. Its effects on blood pressure (BP), heart rate, metabolic functions and renal hormones were analyzed after administration of a single oral morning dose in a 3-phase fashion when administered to 17 patients (11 women, 6 men, 21 to 59 years) with mild to moderate uncomplicated essential hypertension. After titrating the antihypertensive effective dose biweekly from 1 to 8 mg/day and a mean end titration-point dose of 4.14 +/- 0.1 mg (mean +/- standard error of the mean) at week 8 of treatment, it was adjusted to maintain diastolic BP at levels less than or equal to 90 mm Hg for up to 12 weeks of treatment when, at a final mean dose of 4.35 +/- 0.2 mg/day, BP decreased in all patients by a mean 31 +/- 3/17 +/- 2 (supine) and 39 +/- 3/15 +/- 3 (standing) mm Hg (p less than 0.005) with no increase in heart rate and no "first-dose phenomenon." Neither the renin-aldosterone system nor electrolyte excretion was significantly affected. Renal function and metabolic parameters also remained unchanged. Urinary kallikrein excretion was augmented 2.47-fold (p less than 0.002). There was good tolerance; 1 patient discontinued the study because of dry nose. These results suggest that long-term monotherapy with doxazosin is an effective and safe antihypertensive agent for mild to moderate essential hypertension that stimulates urinary kallikrein excretion.
Oliveros-Palacios
M C
MC
Department of Medicine, Universidad del Zulia, Facultad de Medicina, Maracaibo, Venezuela.
Godoy-Godoy
N
N
Colina-Chourio
J A
JA
D000328:Adult; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D004311:Double-Blind Method; D017292:Doxazosin; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D007610:Kallikreins / Q000187:drug effects / Q000652:urine*; D008297:Male; D008875:Middle Aged; D009318:Natriuresis / Q000187:drug effects; D011224:Prazosin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D012084:Renin-Angiotensin System / Q000187:drug effects*
D000959:Antihypertensive Agents; D007610:Kallikreins; D017292:Doxazosin; D011224:Prazosin