Influence of ambient plasma noradrenaline on renal haemodynamics in Type 1 (insulin-dependent) diabetic patients and healthy subjects

Abstract

Imbalances in renal vasodilatory and vasoconstrictive mechanisms are responsible for the renal haemodynamic changes observed in Type 1 diabetes mellitus. Animal experiments have shown that noradrenaline (NA) infusion increases the intraglomerular pressure by predominantly efferent arteriolar vasoconstriction. The relationships between ambient plasma NA levels and renal haemodynamics were studied in 18 healthy control subjects (group C); in 17 normoalbuminuric diabetic patients (group D1) (albumin excretion rate (Ualb V) < 20 μg min⁻¹), and in 17 microalbuminuric Type 1 diabetic patients (group D2) (UalbV 20–200 μg min⁻¹), all patients being without overt autonomic neuropathy. Supine glomerular filtration rate (GFR (ml min⁻¹ 1.73 m⁻²)) and effective renal plasma flow (ERPF (ml min⁻¹ 1.73 m⁻²)) were determined over a 2-h period using constant infusions of ¹²⁵I-iothalamate and ¹³¹I-hippuran, respectively. The subjects were studied in the fasting state. The diabetic patients were investigated during near normoglycaemia. Data are given as means and SD. In group D1, GFR and ERPF (126±15 and 538±89, respectively) were elevated as compared with controls (108±15 and 478±73; p<0.01 and p<0.05, respectively). In group D2, GFR (124±25, p<0.05) but not ERPF (515±104) was higher than in the controls. GFR and ERPF were negatively correlated with venous plasma NA in group C (r= −0.61, p<0.005 and r= −0.64, p<0.001, respectively), in group D1 (r= −0.54, p<0.03 and r= −0.63, p<0.005, respectively) and in group D2 (r=0.53, p<0.03 and r = −0.60, p<0.01, respectively). Multiple regression analysis disclosed that diabetes per se, independent from plasma NA, had a positive contribution to GFR. In contrast, ERPF was only related to plasma NA levels. GFR and ERPF are inversely related to venous plasma NA levels, both in healthy and in diabetic subjects, supporting the hypothesis that plasma NA is a vasoconstrictive substance. The independent positive effect of diabetes as a categorial variable on GFR, suggests that concomitant vasodilating mechanisms play a role in the renal haemodynamic alterations in Type 1 diabetes mellitus.

Key Words:

• effective renal plasma flow
• glomerular filtration rate
• plasma noradrenaline
• Type 1 diabetes mellitus