THE ENHANCED PRESSOR-RESPONSE IN TYPE-2 DIABETES IS NOT BASED UPON A GENERALIZED INCREASE IN VASCULAR RESPONSIVENESS

Objective: The present study was performed to discriminate between cen tral and peripheral effects of noradrenaline (NA) in normotensive, non -obese, type 2 diabetic patients. Methods: Study I: In 10 patients and 10 healthy volunteers (HV) cumulative doses of NA were infused intrav enously until mean arterial pressure (MAP) rose with 20 mmHg, and subs equently the effects on the forearm blood flow (FBF) was measured. Als o, the FBF response to intra-arterial NA (0.025, 0.1, 0.4 mu g min(-1) ) was measured. Study II: In 13 patients and 14 HV the venous constric tor response to a cumulative local infusion of NA in a dorsal hand vei n was determined. Results: In study I the circulating plasma NA concen trations inducing a rise in MAP of 20 mmHg, were lower in the type 2 p atients relative to the HV (p < 0.01). The relationship between change s in pressure and changes in heart rate were similar in both groups. M oreover, FBF responsiveness to intra-arterial NA was not different bet ween the two groups. The slopes of the deltaMAP/NA regression lines we re correlated with basal insulin levels and relative insulin resistanc e in the healthy volunteers (R = 0.77, p < 0.01, and R = 0.83, p < 0.0 1), but not in the type 2 diabetic patients. In study II no difference s were observed in the dose generating half maximum (ED50) and the max imum (E-max) response to NA between the type 2 patients and the HV. Co nclusions: Non-obese normotensive type 2 patients have an increased pr esser response to NA, which is not based upon a defect in skeletal mus cle resistance arterioles, peripheral veins, or a defect in the barore ceptor system. Therefore, in type 2 diabetes the noradrenergic respons iveness of other vascular beds, such as the splanchnic or renal, must be enhanced. (C) 1998 Elsevier Science B.V.