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 central and peripheral effects of noradrenaline (NA) in normotensive, non-obese, type 2 diabetic patients.


METHODS
Study I: In 10 patients and 10 healthy volunteer (HV) cumulative doses of NA were infused intravenously until mean arterial pressure (MAP) rose with 20 mmHg, and subsequently the effects on the forearm blood flow (FBF) was measured. Also, the FBF response to intra-arterial NA (0.025, 0.1, 0.4 micrograms min-1) was measured. Study II: In 13 patients and 14 HV the venous constrictor response to a cumulative local infusion of NA in a dorsal hand vein was determined.


RESULTS
In study I the circulating plasma NA concentrations inducing a rise in MAP of 20 mmHg, were lower in the type 2 patients relative to the HV (p < 0.01). The relationship between changes in pressure and changes in heart rate were similar in both groups. Moreover, FBF responsiveness to intra-arterial NA was not different between the two groups. The slopes of the delta MAP/NA regression lines were correlated with basal insulin levels and relative insulin resistance in the healthy volunteers (R = 0.77, p < 0.01, and R = 0.83, p < 0.01), but not in the type 2 diabetic patients. In study II no differences were observed in the dose generating half maximum (ED50) and the maximum (Emax) response to NA between the type 2 patients and the HV.


CONCLUSIONS
Non-obese normotensive type 2 patients have an increased pressor response to NA, which is not based upon a defect in skeletal muscle resistance arterioles, peripheral veins, or a defect in the baroreceptor system. Therefore, in type 2 diabetes the noradrenergic responsiveness of other vascular beds, such as the splanchnic or renal, must be enhanced.
Dept. of Internal Medicine, Cardiovascular Research Institute Maastricht, University Hospital Maastricht, Netherlands.
F C
FC
Huvers
P W
PW
de Leeuw
C H
CH
de Haan
A J
AJ
Houben
C
C
Buijs
N C
NC
Schaper
D001794:Blood Pressure / Q000187:drug effects*; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005542:Forearm / Q000098:blood supply; D006225:Hand / Q000098:blood supply; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D007269:Injections, Intra-Arterial; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000008:administration & dosage / Q000494:pharmacology*; D012039:Regional Blood Flow / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000008:administration & dosage / Q000494:pharmacology*
D014662:Vasoconstrictor Agents; D009638:Norepinephrine