CHLOROQUINE-INDUCED VENODILATION IN HUMAN HAND VEINS

Objective: Hypotension induced by parenteral administration of chloroq uine is a common and serious adverse effect of this drug. Our aim was to investigate whether chloroquine produces venodilation in vivo and t o explore the underlying mechanisms, Methods: Vascular effects of chlo roquine were studied in healthy volunteers with use of the dorsal hand vein technique at the Geriatric Research Education and Clinical Cente r, Veterans Affairs Pale Alto Health Care System, We studied 22 health y volunteers (19 men and three women). Venous responsiveness was deter mined with the dorsal hand vein technique, which measures the diameter of the vein. Results: Chloroquine was found to produce a dose-depende nt relaxation of hand veins preconstricted with the alpha(1)-receptor selective agonist phenylephrine, The venodilatory response to chloroqu ine ranged from 15% +/- 19% at an infusion rate of 0.75 mu g/min to 61 % +/- 24% at 48 mu g/min. Venodilation was attenuated by the nitric-ox ide synthase inhibitor N-G-monomethyl-L-arginine (L-NMMA) so that the dose of chloroquine required to produce 20% venodilation was increased from 3.7 mu g/min to 15 mu g/min (p < 0.01). In the presence of a com bination of histamine receptor antagonists, there was also a diminutio n of the vasodilatory response to chloroquine from 72% +/- 5% to 44% /- 5% at the infusion rate of 96 mu g/min. The response was further re duced to 33% +/- 7% by the coinfusion of H-1-/H-2-receptor antagonists with L-NMMA. Conclusion: Chloroquine produces venodilation at infusio n rates that achieve local concentrations likely similar to those obse rved systemically after clinically relevant intravenous doses. The dat a also suggest a role for nitric oxide and histamine release in mediat ing this response.