Effects of doxazosin on ambulatory blood pressure and sympathetic nervous activity in hypertensive Type 2 diabetic patients with overt nephropathy

Abstract

Few studies have reported the effect of alpha(1)-adrenergic antagonists on 24-h blood pressure (BP) and sympathetic nervous activity in hypertensive patients with diabetic nephropathy. We assessed the effects of doxazosin on 24-h BP and spectral analysis of heart rate variability in hypertensive Type 2 diabetic patients with macroalbuminuria and compared the results with those in hypertensive Type 2 diabetic patients with normoalbuminuria and non-diabetic patients with essential hypertension. Thirty-three patients in the macroalbuminuric group, 24 patients in the normoalbuminuric group, and 34 patients with essential hypertension underwent ambulatory BP monitoring before and after doxazosin treatment. Spectral analysis was performed to calculate the high-frequency (HF) components, a marker of parasympathetic nervous activity, and the low-frequency (LF) components, a marker of sympathetic nervous activity. Doxazosin decreased waking (from 158 +/- 17/88 +/- 10 to 148 +/- 15/80 +/- 7 mmHg, P = 0.001 for systolic and P < 0.001 for diastolic BP) and sleeping BP (146 +/- 20/79 +/- 10 to 137 +/- 17/72 +/- 9 mmHg, P < 0.001 and P < 0.001) in the macroalbuminuric group, but only decreased waking BP in the essential hypertension group (157 +/- 16/91 +/- 9 to 145 +/- 15/84 +/- 11 mmHg, P < 0.001 and P < 0.001) and normoalbuminuric group (159 +/- 15/89 +/- 9 to 150 +/- 16/82 +/- 10 mmHg, P = 0.014 and P < 0.001). Doxazosin decreased waking (from 1.48 +/- 0.11 to 1.42 +/- 0.12, P = 0.001) and sleeping (1.46 +/- 0.11 to 1.40 +/- 0.13, P = 0.001) LF components [unit: log(ms(2)/Hz)] only in the macroalbuminuric group without changing HF components. The normoalbuminuric and essential hypertension groups showed no differences (P = 0.637 and 0.492) in LF components during sleep. Doxazosin may be an antihypertensive agent that decreases both waking and sleeping BP through inhibiting sympathetic nervous activity in macroalbuminuric diabetes patients.