Hemodynamic and humoral effects of the angiotensin II antagonist losartan in essential hypertension.
Losartan (DuP 753) is a novel orally active angiotensin II antagonist that lowers blood pressure. The present study evaluates the hemodynamic and humoral effects of losartan in essential hypertension. Fifteen patients (12 men, 3 women; mean age, 46 +/- 2 years; range, 33 to 64 years) with a diastolic blood pressure (DBP) between 95 and 115 mm Hg after 2 weeks of placebo participated in the study. Initially the patients were treated with losartan (50 mg) once daily for 1 month. Then, if the trough DBP was > or = 93 mm Hg, hydrochlorothiazide (HCTZ), 6.25 to 12.5 mg daily, and nifedipine, 30 to 60 mg daily, were added as needed. Ten patients completed 12 months of treatment. Trough blood pressure, heart rate, plasma creatinine, potassium, uric acid, cholesterol, renin activity (PRA), aldosterone, and norepinephrine were measured at baseline and after 1 and 12 months of treatment. Losartan lowered mean arterial pressure significantly from 119 +/- 2 mm Hg at baseline to 113 +/- 2 mm Hg (P < .05) after 1 month of treatment. Coadministration of HCTZ and nifedipine further decreased the mean arterial pressure to 103 +/- 2 mm Hg after 12 months of treatment. Plasma levels of creatinine, potassium, uric acid, cholesterol, and norepinephrine remained unchanged. PRA increased and plasma aldosterone decreased significantly (P < .05). The decrease in mean arterial pressure was related to baseline PRA (r = 0.53, P < .05). and to the change in PRA (r = 0.52, P < .05).(ABSTRACT TRUNCATED AT 250 WORDS)
Grossman
E
E
Chorley Hypertension Unit, Chaim Sheba Medical Center, Tel Hashomer, Israel.
Peleg
E
E
Carroll
J
J
Shamiss
A
A
Rosenthal
T
T
D000328:Adult; D000450:Aldosterone / Q000097:blood; D000804:Angiotensin II / Q000037:antagonists & inhibitors*; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001713:Biphenyl Compounds / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000502:physiology; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D006852:Hydrochlorothiazide / Q000627:therapeutic use; D006973:Hypertension / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D007093:Imidazoles / Q000627:therapeutic use*; D019808:Losartan; D008297:Male; D008875:Middle Aged; D018377:Neurotransmitter Agents / Q000097:blood*; D009543:Nifedipine / Q000627:therapeutic use; D009638:Norepinephrine / Q000097:blood; D012083:Renin / Q000097:blood; D013777:Tetrazoles / Q000627:therapeutic use*
D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D007093:Imidazoles; D018377:Neurotransmitter Agents; D013777:Tetrazoles; D006852:Hydrochlorothiazide; D000804:Angiotensin II; D000450:Aldosterone; D012083:Renin; D009543:Nifedipine; D019808:Losartan; D009638:Norepinephrine