Pharmacodynamics of L-NMMA in type 1 diabetes patients and control subjects.

Abstract

RATIONALE: 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.