Angiotensin II in human veins: Development of rapid desensitization and effect of indomethacin

1. The present study investigated whether rapid desensitization (tachyphyla xis) develops after exposure of human hand veins to angiotensin (Ang)II and whether pretreatment with indomethacin affects its development. 2, Venoconstrictor responses to increasing (2-256 ng/min) and constant (50 ng/min) doses of AngII and noradrenaline (NA) infusion were obtained in six healthy male subjects using the dorsal hand vein technique. After pretreat ment with indomethacin and placebo, venoconstrictor responses to 50 ng/min Angn infusion were obtained in eight healthy male subjects. 3, The maximal mean (+/-SD) venoconstrictor response to NA (obtained with 2 56 ng/min NA) was 93.1+/-4.7%, whereas that to AngII (obtained with doses b etween 16 and 128 ng/min) was 43.8+/-12.2%. Continuous infusion of NA induc ed constant venoconstriction, whereas the venoconstrictor response to AngII peaked 3 min after the beginning of infusion and, thereafter, was attenuat ed. 4, Venoconstriction in response to constant Angn. infusion after indomethac in pretreatment was significantly larger than that after placebo from 6 to 18 min after the initiation of infusion. 5, These findings show that rapid desensitization to AngII develops in huma n hand veins and this is compatible with the hypothesis that vasodilator pr ostaglandins are involved in the development of this desensitization.