The Effect of Glibornuride on Plasma Atrial Natriuretic Factor Levels in Patients with Newly Diagnosed NIDDM

The aim of this clinical trial was to study the participation of plasma atrial natriuretic factor (ANF) in the risk of developing diabetic nephropathy by increasing the intraglomerular pressure. The effect of glibornuride on the plasma ANF levels and natriuresis was estimated in 10 newly diagnosed NIDDM patients and 10 control subjects. At base line, plasma ANF levels (15.05+/-2.32 pg/ml and 11.13+/-0.85 pg/ml) and the urinary sodium and potassium excretion rates were similar in patients and control subjects, respectively. Similarly, intravenous saline infusion (2 mmol/kg/60 min) resulted in remarkable elevation of plasma ANF levels in patients and in controls (28.89+/-4.72 pg/ml and 20.18+/-2.48 pg/ml, respectively) and in increased urinary sodium and potassium excretion rates in both groups. In contrast, after a single dose of 50 mg glibornuride p.o. the saline infusion did not increase ANF levels (15.13+/-1.00 pg/ml), while natriuresis but not kaliuresis persisted. All tests were performed during euglycemic clamp. It was suggested that glibornuride, with its natriuretic effect through the ATP sensitive potassium channels on the apical membrane of the thick ascending limb of loop of Henle and cortical collecting duct cells might inhibit the elevation of plasma ANF levels in response to extracellular fluid volume expansion. Similarly, with its natriuretic effect, it protects the diabetic patients against possible sodium retention. This result is considered noteworthy, since the inhibition of plasma ANF elevation in early diabetes by glibornuride may prevent glomerular hypertension and subsequent development of nephropathy.