Pharmacodynamics of L-NMMA in type 1 diabetes patients and control subjects.
BACKGROUND
L-NMMA is widely used in venous occlusion plethysmography studies to determine baseline NO production. Studies using L-NMMA indicate that endothelial dysfunction is present early in the course of diabetic microvascular complications. However, the optimal dose to maximally inhibit NO-production is unknown.


OBJECTIVE
To determine the L-NMMA-dose that maximally reduces basal forearm blood flow (FBF). To investigate whether there are any differences in the response to L-NMMA between non-complicated type 1 diabetes patients and control subjects.


METHODS
In eight non-complicated type 1 diabetes patients and nine healthy subjects FBF-responses to intra-arterial infusion of increasing doses of L-NMMA (0.01-1.6 mg/min/dL forearm volume [FAV]) were measured using the perfused forearm technique.


RESULTS
Infusion of 0.8 mg/min/dL maximally reduced FBF. The dose of 1.6 mg/min/dL did not additionally reduce FBF. No differences existed between non-complicated type 1 diabetes patients and controls with regard to EC50 (0.017 +/- 0.02 resp. 0.22 +/- 0.02 mg L-NMMA/min/dL) or maximal vasoconstrictive response (Delta FBF: 1.13 +/- 0.4 resp. 0.97 +/- 0.4 mL/min/dL). Throughout the study blood pressure increased significantly in both groups, possibly reflecting a systemic vasoconstrictive effect of L-NMMA.


CONCLUSIONS
The maximal vasoconstrictive dose was 0.8 mg/min/dL in type 1 diabetes patients as well as the control subjects. There were no significant differences between non-complicated type 1 diabetes subjects and controls with regard to the pharmacodynamics of L-NMMA. At high dosages of L-NMMA a systemic effect can not be ruled out.
Veldman
B A J
BA
Department of Internal Medicine, University Medical Center St. Radboud, Nijmegen, The Netherlands.
Waanders
M
M
Smits
P
P
D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D015992:Body Mass Index; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004341:Drug Evaluation / Q000379:methods; D005260:Female; D005542:Forearm / Q000098:blood supply; D006801:Humans; D007261:Infusions, Intra-Arterial; D008297:Male; D010991:Plethysmography / Q000706:statistics & numerical data; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology; D013997:Time Factors; D019323:omega-N-Methylarginine / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use
D001786:Blood Glucose; D019323:omega-N-Methylarginine