Exaggerated Sensitivity to NE-Induced Vasoconstriction in IDDM Patients With Microalbuminuria: Possible Etiology and Diagnostic Implications

Abstract

Increased urinary albumin excretion rate (AER) in the microalbuminuric phase of diabetic nephropathy has been attributed to intraglomerular hypertension. This could be caused by constriction of efferent glomerular arterioles, which carry α-adrenoceptors. We tested the hypothesis that insulin-dependent diabetes mellitus (IDDM) patients with microalbuminuria are hypersensitive to vasoconstriction induced by norepinephrine (NE). We studied 15 IDDM patients with microalbuminuria (AER 32–295 mg/24 h), 13 IDDM patients with normal AER (5–24 mg/24 h), and 9 nondiabetic subjects (AER 8–22 mg/24 h). All were normotensive. NE-induced vasoconstriction was measured in dorsal hand veins, which carry α-receptors similar to those of glomerular efferent arterioles. Vein diameter was measured with a linear displacement probe during a stepped NE infusion (1–32 ng/min) into the vein, and venoconstriction was expressed as a percentage of the maximum passively distended venous diameter. Microalbuminuric IDDM patients exhibited significantly greater vasoconstriction (P < 0.005) at all NE infusion rates than both other groups. The NE infusion rate producing 50% of maximal venoconstriction (ED50) in the microalbuminuric IDDM group (median 1.1 ng/min, range 0.2–25.2 ng/min) was significantly less than in both the normoalbuminuric IDDM group (median 12.5 ng/min, range 4.9–40.5 ng/min, P = 0.00007) and the nondiabetic group (median 17.7 ng/min, range 5.9–42.2 ng/min, P = 0.0003). Dose-response curves and ED50 did not differ significantly between normalbuminuric IDDM and nondiabetic groups. IDDM patients with microalbuminuria are hypersensitive to NE-induced vasoconstriction. Such an abnormality in efferent glomerular arterioles could contribute to albuminuria and, if affecting the systemic resistance vessels, to the hypertension that coexists with later phases of nephropathy. This test may help identify at an early stage IDDM patients at risk of developing nephropathy.