Effects of losartan and amlodipine on urinary albumin excretion and ambulatory blood pressure in hypertensive type 2 diabetic patients with overt nephropathy.
OBJECTIVE
Few studies have assessed whether 24-h blood pressure control induced by antihypertensive agents improves macroalbuminuria in hypertensive type 2 diabetic patients with overt nephropathy. We evaluated the effects of losartan and amlodipine on 24-h blood pressure, autonomic nervous activity, and albuminuria in these patients.


METHODS
In this open-label, parallel-prospective, randomized study, 44 patients were treated with losartan and 43 with amlodipine for a 12-week titration phase and a maintenance phase for a maximum of 12 weeks. Twenty-four-hour blood pressure and urinary albumin excretion were measured before and during treatment. Simultaneously, power spectral analysis of heart rate was performed to evaluate low frequency (LF) and high frequency (HF) components and LF-to-HF ratios as an index of sympathovagal balance.


RESULTS
Losartan decreased (P < 0.001) mean blood pressure from 162/91 to 150/82 mmHg during daytime and from 146/82 to 137/74 mmHg during nighttime (systolic/diastolic). Amlodipine also decreased (P < 0.001) blood pressure from 159/90 to 147/82 mmHg during daytime and from 143/81 to 131/72 mmHg during nighttime. LF and HF components and nighttime-to-daytime ratios for the LF-to-HF ratios did not differ during treatment in two groups, showing no changes in the diurnal autonomic nervous rhythm. Losartan decreased (P < 0.001) 24-h urinary albumin excretion from 810 mg/day (95% CI 780-1,140) to 570 (510-910). Amlodipine, however, did not decrease (P = 0.893) albuminuria (790 mg/day [780-1,170] vs.790 [710-1,260]).


CONCLUSIONS
These results suggest that in type 2 diabetes with overt nephropathy, 24-h blood pressure regulation alone is inadequate to reduce macroalbuminuria and additional effects of losartan are crucial for antiproteinuric action.
Yasuda
Gen
G
Second Department of Internal Medicine, Division of Nephrology, Yokohama City University School of Medicine, 4-57 Urafune, Minami-ku, Yokohama 232-0024, Japan. y911429@urahp.yokohama-cu.ac.jp
Ando
Daisaku
D
Hirawa
Nobuhito
N
Umemura
Satoshi
S
Tochikubo
Osamu
O
D000328:Adult; D000419:Albuminuria / Q000652:urine*; D017311:Amlodipine / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects*; D018660:Blood Pressure Monitoring, Ambulatory; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology* / Q000652:urine; D003925:Diabetic Angiopathies / Q000188:drug therapy* / Q000503:physiopathology / Q000652:urine; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology / Q000652:urine; D019808:Losartan / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged
D000959:Antihypertensive Agents; D017311:Amlodipine; D019808:Losartan