CHAPTER 3 INFLUENCE OF AMBIENT PLASMA NOREPINEPHRINE ON RENAL HAEMODYNAMICS IN IDDM PATIENTS AND HEALTHY SUBJECTS

3 1 Imbalances in renal vasodilatory and vasoconstrictive mechanisms are responsible for the renal haemodynamic changes observed in IDDM patients. Animal experiments have shown that norepinephrine (NE) infusion increases the intraglomerular pressure by predominantly efferen t arteriolar vasoconstriction. The relationships between ambient plasma NE levels and rena l haemodynamics were studied in 18 healthy control subjects (group C), in 17 normoalbuminuri c (albumin excretion rate (Ualb.V) <20 µg/min; group D1) and in 17 microalbuminuric (Ualb.V 20-200 µg/min; group D2) IDDM patients without overt autonomic neuropathy. Supine glomerular filtration rate (GFR (ml/min per 1.73m )) and effective renal plasma flow (ERPF (ml/min per 1.73m )) were 2 2 determined over a 2 h period using constant infusions of I-iothalamate and I-hippuran, respec- 125 131 tively. The subjects were studied in the fasti ng state. The IDDM patients were investigated during near normoglycaemia. Data are given as means±SD. In group D1, GFR and ERPF (126±15 and 538±89, respectively) were elevated as compared to group C (108±15 and 478±73; p<0.01 and p<0.05, respec- tively). In group D2, GFR (124±25, p<0.05) but not ERPF (515±104) was higher than in group C. GFR and ERPF were negatively correlated with venous plasma NE in 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 tha t diabetes per se, independent from plasma NE, had a positive contribution to GFR. In contrast, ERPF was only related to plasma NE levels. In conclusion, GFR and ERPF are inversely related to venous plasma NE levels both in healthy and in IDDM subjects, supporting the hypothesis that plasma NE 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 haemodynami c alterations in IDDM patients.