Chloroquine-induced venodilation in human hand veins

Hypotension induced by parenteral administration of chloroquine is a common and serious adverse effect of this drug. Our aim was to investigate whether chloroquine produces venodilation in vivo and to explore the underlying mechanisms.

Vascular effects of chloroquine were studied in healthy volunteers with use of the dorsal hand vein technique at the Geriatric Research Education and Clinical Center, Veterans Affairs Palo Alto Health Care System. We studied 22 healthy volunteers (19 men and three women). Venous responsiveness was determined with the dorsal hand vein technique, which measures the diameter of the vein.

Chloroquine was found to produce a dose-dependent relaxation of hand veins preconstricted with the alpha 1-receptor selective agonist phenylephrine. The venodilatory response to chloroquine ranged from 15% +/- 19% at an infusion rate of 0.75 microgram/min to 61% +/- 24% at 48 microgram/min. Venodilation was attenuated by the nitric-oxide synthase inhibitor NG-monomethyl-L-arginine (L-NMMA) so that the dose of chloroquine required to produce 20% venodilation was increased from 3.7 micrograms/min to 15 micrograms/min (p < 0.01). In the presence of a combination of histamine receptor antagonists, there was also a diminution of the vasodilatory response to chloroquine from 72% +/- 5% to 44% +/- 5% at the infusion rate of 96 micrograms/min. The response was further reduced to 33% +/- 7% by the coinfusion of H1-/H2-receptor antagonists with L-NMMA.

Chloroquine produces venodilation at infusion rates that achieve local concentrations likely similar to those observed systemically after clinically relevant intravenous doses. The date also suggest a role for nitric oxide and histamine release in mediating this response.