Tetrahydrobiopterin improves endothelium-dependent vasodilation by increasing nitric oxide activity in patients with Type II diabetes mellitus.
OBJECTIVE
Tetrahydrobiopterin is an essential cofactor of nitric oxide synthase, and its deficiency decreases nitric oxide bioactivity. Our aim was to find whether supplementation of tetrahydrobiopterin could improve endothelial dysfunction in diabetic patients.


METHODS
Forearm blood flow responses to the endothelium-dependent vasodilator acetylcholine (0.75-3.0 microg x 100 ml(-1) x min(-1)) and to the endothelium-independent vasodilator sodium nitroprusside (0.1-1.0 microg x 100 ml(-1) x min(-1)) before and during concomitant intra-arterial infusion of tetrahydrobiopterin (500 microg/min) were measured by venous occlusion plethysmography in 12 control subjects and 23 patients with Type II (non-insulin-dependent) diabetes mellitus.


RESULTS
In control subjects, tetrahydrobiopterin had no effect on the dose-response curves to acetylcholine and sodium nitroprusside. In contrast, in diabetic patients, the attenuated endothelium-dependent vasodilation to acetylcholine was considerably improved by concomitant treatment with tetrahydrobiopterin, whereas the endothelium-independent vasodilation was not affected. This beneficial effect of tetrahydrobiopterin in diabetic patients could be completely blocked by N(G)-monomethyl-L-arginine.


CONCLUSIONS
These findings suggest the possibility that endothelial dysfunction in Type II diabetes might be related to decreased availability of tetrahydrobiopterin.
Heitzer
T
T
University Hospital Clinic Hamburg-Eppendorf, Department of Cardiology, Clinic for Internal Medicine, Germany.
Krohn
K
K
Albers
S
S
Meinertz
T
T
D000109:Acetylcholine / Q000494:pharmacology; D001708:Biopterins / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology* / Q000627:therapeutic use; D001783:Blood Flow Velocity; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005542:Forearm / Q000098:blood supply; D006801:Humans; D007261:Infusions, Intra-Arterial; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009599:Nitroprusside / Q000494:pharmacology; D010991:Plethysmography; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology; D019323:omega-N-Methylarginine / Q000494:pharmacology
D004791:Enzyme Inhibitors; D014665:Vasodilator Agents; D009599:Nitroprusside; D001708:Biopterins; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; C003402:sapropterin; D000109:Acetylcholine