EFFECT OF ALPHA-ADRENERGIC BLOCKERS, ACE-INHIBITORS, AND CALCIUM-CHANNEL ANTAGONISTS ON RENAL-FUNCTION IN HYPERTENSIVE NON-INSULIN-DEPENDENT DIABETIC-PATIENTS

In the present study we investigated the effect of a selective alpha(1 )-adrenergic blocker (doxazosin), an angiotensin-converting enzyme (AC E) inhibitor (captopril), and a calcium channel antagonist (nifedipine ) on renal function in hypertensive non-insulin-dependent diabetic pat ients. 30 NIDD hypertensive patients (age = 50 +/- 3 years; BMI = 30 /- 1 kg/m(2))(mean +/- SEM) were studied before and after a 12-week pe riod of antihypertensive treatment. Ten patients were treated with dox azosin (Cardura) (2-8 mg once daily or 8 mg b.i.d.), 9 with captopril (Capoten) (25-50 mg b.i.d.), and 11 with nifedipine (Procardia-XL) (30 -60 mg once daily). Blood pressure, creatinine clearance, 24-hour urin ary protein excretion, fasting plasma glucose concentration and glycos ylated hemoglobin were measured before and after drug treatment. Easti ng plasma glucose and glycosylated hemoglobin (HbA(1c)) were similar i n all three groups prior to the start of antihypertensive therapy and did not change significantly from baselline in any treatment groups. I n the doxazosin group creatinine clearance rose from 99 +/- 8 to 122 /- 8 ml/1.73 m(2) . min (p < 0.01), while 24-hour urinary protein excr etion declined from 2.66 +/- 0.05 to 1.76 +/- 0.02 mg/day/ml/1.73 m(2) . min (p < 0.01). In diabetics treated with captopril creatinine clea rance rose from 93 +/- 6 to 109 +/- 9 ml/1.73 m(2) . min (p < 0.05), w hile the 24-hour urinary protein excretion fell from 2.70 +/- 0.05 to 2.03 +/- 0.04 mg/day/ml/1.73 m(2) . min (p < 0.05). In patients treate d with nifedipine creatinine clearance did not change (97 +/- 6 vs. 94 +/- 7 ml/1.73 m(2) . min), while 24-hour urinary protein excretion de creased from 2.84 +/- 0.04 to 1.95 +/- 0.03 mg/day/ml/1.73 m(2) . min. Systolic and diastolic blood pressure were similar in doxazosin (150 +/- 3/95 +/- 2 mm Hg), captopril(153 +/- 3/93 +/- 1), and nifedipine ( 155 +/- 4/93 +/- 1) groups prior to the start of antihypertensive ther apy and declined to 143 +/- 3/84 +/- 3 (doxazosin), 139 +/- 3/82 +/- 3 (captopril), and 141 +/- 3/84 +/- 1 (nifedipine) mm Hg (all p < 0.01 vs. pretreatment). In summary, both doxazosin and captopril treatment were associated with significant rises in GFR, while all three antihyp ertensive agents caused a significant decline in proteinuria. These re sults indicate that alpha-adrenergic blockers, ACE inhibitors, and cal cium channel antagonists can safely and effectively be used in the cli nical management of non-insulin-dependent diabetic patients with hyper tension.