Hand vein responses to noradrenaline in normotensive patients with insulin-dependent diabetes mellitus and microalbuminuria: Effects of alpha-adrenoceptor blockade with doxazosin

Nephropathy commonly develops in patients with insulin-dependent (type 1) d iabetes. Administration of an antihypertensive agent to type 1 diabetes pat ients with microalbuminuria, the first clinically delectable stage of nephr opathy, can help slow renal deterioration. It is postulated that the exagge rated vasoconstrictor response to noradrenaline seen in these patients may be relevant in the development of microalbuminuria. This open, non-comparat ive pilot study was designed to investigate the effects of the alpha(1)-adr enoceptor antagonist doxazosin on noradrenaline-induced hand vein vasoconst riction and on albumin excretion in 14 normotensive type 1 diabetes patient s with microalbuminuria. After a three-week placebo run-in period, patients received doxazosin (1, 2, and then 4 mg once-daily, at two-week intervals) for six weeks, followed by a two-week placebo washout period. Vasoconstric tor responses to noradrenaline were measured in dorsal hand veins at the en d of each two-week period. Hand vein vasoconstrictor responses to noradrena line decreased significantly, compared with placebo, at 4 mg/day doxazosin (p = 0.006). The mean albumin excretion rate was lower than baseline at all doses of doxazosin, but changes did Mot reach statistical significance. Do xazosin was generally well-tolerated;four patients (29%) reported mild-to-m oderate treatment-related adverse events. This study indicates that alpha(1 )-adrenoceptor blockade can blunt the exaggerated vascular reactivity to no radrenaline in normotensive type I diabetes patients with microalbuminuria, and supports further research into It potential role for doxazosin in prev enting the development of diabetic nephropathy.