nitrophenols and Albuminuria

The aim of this study was to assess the effects of irbesartan alone and combined with amlodipine, efonidipine, or trichlormethiazide on blood pressure (BP) and urinary albumin (UA) excretion in hypertensive patients with microalbuminuria (30≤UA/creatinine (Cr) ratio [UACR] <300 mg/g Cr) and upper-normal microalbuminuria (10≤UACR<30 mg/g Cr). This randomized controlled trial enrolled 175 newly diagnosed and untreated hypertensive patients (home systolic blood pressure [SBP]≥135 mmHg; 10≤UACR<300 mg/g Cr of casual spot urine at the first visit to clinic). All patients were treated with irbesartan (week 0). Patients who failed to achieve home SBP ≤125 mmHg on 8-week irbesartan monotherapy (nonresponders, n = 115) were randomized into three additional drug treatment groups: trichlormethiazide (n = 42), efonidipine (n = 39), or amlodipine (n = 34). Irbesartan monotherapy decreased home SBP and first morning urine samples (morning UACR) for 8 weeks (p < 0.0001). At 8 weeks after randomization, all three additional drugs decreased home SBP (p < 0.0002) and trichlormethiazide significantly decreased morning UACR (p = 0.03). Amlodipine decreased morning UACR in patients with microalbuminuria based on casual spot urine samples (p = 0.048). However, multivariate analysis showed that only higher home SBP and UACR at week 8, but not any additional treatments, were significantly associated with UACR reduction between week 8 and week 16. In conclusion, crucial points of the effects of combination therapy on UACR were basal UACR and SBP levels. The effect of trichlormethiazide or amlodipine treatment in combination with irbesartan treatment on microalbuminuria needs to be reexamined based on a larger sample size after considering basal UACR and SBP levels.

Topics: Aged; Albuminuria; Amlodipine; Antihypertensive Agents; Biphenyl Compounds; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Dihydropyridines; Drug Therapy, Combination; Essential Hypertension; Female; Humans; Irbesartan; Male; Middle Aged; Nitrophenols; Organophosphorus Compounds; Tetrazoles; Trichlormethiazide; Urinalysis

We investigated the renal protective effect of nifedipine (2-nitrophenyl derivative BAY a 1040) in streptozotocin (STZ)-induced spontaneously hypertensive rats (SHRs, 8 weeks of age). Diabetic SHRs were treated with 40 mg/kg/day of nifedipine or efonidipine as controls for 16 weeks. Dosage of nifedipine or efonidipine was chosen after preliminary studies demonstrated that it showed moderate antihypertensive action (more than a 20% decrease in systemic blood pressure after treatment). In the diabetic SHR, the excretion of urinary albumin was increased and reached 4.41 +/- 0.08 mg/day at 24 weeks. The levels of urinary albumin in the diabetic SHR after treatment with nifedipine were significantly less than those in the diabetic SHR at 24 weeks (p < 0.01). Levels of the ratio of creatinine clearance to body weight were significantly decreased in the diabetic SHR after treatment with nifedipine. In light microscopy, the ratio of glomerular tufts to Bowman's areas was significantly decreased compared with those in the diabetic SHRs (p < 0.05). These findings suggest that nifedipine inhibits the development of albuminuria and glomerular enlargement in STZ-induced diabetic SHRs. There was no significant difference in the changes in antihypertensive or antialbuminuric effects between nifedipine and efonidipine. Thus, nifedipine, as well as efonidipine, may become a useful antihypertensive drug with a renal protective effect.

Topics: Albuminuria; Animals; Antihypertensive Agents; Creatinine; Diabetes Mellitus, Experimental; Diabetic Nephropathies; Dihydropyridines; Kidney; Male; Nifedipine; Nitrophenols; Organophosphorus Compounds; Rats; Rats, Inbred SHR; Time Factors; Vasodilator Agents

1. We investigated the renal protective effect of efonidipine hydrochloride (efonidipine, NZ-105) in STZ-induced spontaneously hypertensive rats (SHRs, 8 weeks of age). Diabetic SHRs were treated with 15 mg/kg/day of efonidipine for 12 weeks. 2. The dosage of efonidipine was chosen after preliminary studies demonstrated that it showed mild antihypertensive action (within 20% decrease of systemic blood pressure). 3. In the diabetic SHRs, the excretion of urinary albumin was increased (1.78 +/- 0.09 mg/day) at 4 weeks and reached 4.41 +/- 0.12 mg/day at 12 weeks. The levels of urinary albumin in the diabetic SHRs after treatment with efonidipine were significantly less than those in the diabetic SHRs at 8 and 12 weeks (P < 0.01). 4. Levels of creatinine clearance were decreased in the diabetic SHRs after treatment with efonidipine. 5. In light microscopy, the ratio of glomerular tuft to Bowman's areas was significantly decreased compared with those in the diabetic SHRs (P < 0.05). 6. These findings suggest that efonidipine inhibits the development of albuminuria and glomerular enlargement in the streptozotocin-induced diabetic SHRs and may become a useful antihypertensive drug with a renal protective effect.

Topics: Albuminuria; Animals; Antihypertensive Agents; Diabetes Mellitus, Experimental; Dihydropyridines; Hypertension; Kidney; Male; Nitrophenols; Organophosphorus Compounds; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Streptozocin