Heparin-induced vasodilation in human hand veins.
OBJECTIVE
To investigate whether heparin produces vasodilation in human veins and to explore the underlying mechanisms.


METHODS
Eleven healthy volunteers were studied with the dorsal hand vein compliance technique. Dose-response curves to heparin and enoxaparin were generated. Dose-response curves to heparin were also constructed before and after heparin was infused with the nitric oxide synthase inhibitor N(G)-monomethyl-l-arginine (L-NMMA) or combined histamine H1- and H2-receptor blockade.


RESULTS
Heparin but not enoxaparin caused significant dose-dependent relaxation with an average apparent maximal response (at an infusion rate of 20 IU/min) of 47% +/- 23%. L-NMMA attenuated heparin-induced relaxation (P < .001). The combination of H1-and H2-receptor antagonists attenuated heparin-induced relaxation to a lesser extent (P < .05). Heparin-induced relaxation decreased by 52%, 73%, and 35% in the presence of L-NMMA, indomethacin (INN, indometacin) plus L-NMMA, and combined H1- and H2-receptor blockade, respectively.


CONCLUSIONS
Heparin is an endothelium-dependent venodilator in humans. The mechanism of heparin-induced relaxation involves an increased availability of nitric oxide, possibly partially related to local release of histamine.
Tangphao
O
O
Department of Medicine, Stanford University School of Medicine, Calif, USA.
Chalon
S
S
Moreno
H J
HJ
Abiose
A K
AK
Blaschke
T F
TF
Hoffman
B B
BB
D000328:Adult; D000925:Anticoagulants / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D017984:Enoxaparin / Q000494:pharmacology; D005260:Female; D006225:Hand / Q000098:blood supply*; D006493:Heparin / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D008297:Male; D012016:Reference Values; D014664:Vasodilation / Q000187:drug effects*; D014680:Veins / Q000187:drug effects; D014838:Volunteers
D000925:Anticoagulants; D017984:Enoxaparin; D006493:Heparin