K. Harada et al., Angiotensin II in human veins: Development of rapid desensitization and effect of indomethacin, CLIN EXP PH, 26(12), 1999, pp. 959-963
Citations number
33
Categorie Soggetti
Pharmacology & Toxicology
Journal title
CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY
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.