Objectives: To study whether arginine vasopressin (AVP)
can stimulate endothelin production and/or release <i>in vivo</i>, in the human forearm vasculature.
Design: The effect of the infusion of AVP into the brachial artery on endothelin production across the human forearm vascular bed was studied in healthy male volunteers, and was compared with intra-arterial
infusion of placebo. In another group the effects of AVP
on endothelin production were studied after a prior infusion of L-N<sup>G</sup>-monomethyl-arginine (L-NMMA), a nitric oxide-synthase inhibitor. In a fourth group the effect of L-NMMA alone, without AVP infusion, on endothelin production was studied.
Methods: We measured the effects of AVP, placebo,
L-NMMA followed by AVP and L-NMMA followed by placebo on arterial and venous endothelin concentrations
in the forearm of four groups, each consisting of five
healthy male volunteers. Forearm blood flow was measured by strain gauge plethysmography. The endothelin production was calculated as forearm blood flow times (venous - arterial) endothelin concentration.
Results: The group infused with L-NMMA followed by
infusion of 8 ng AVP/min per dl forearm volume showed
a significant rise in endothelin production from 1.3 (1.8)
to 5.0 (2.0) pg/min/dl at 15 minutes (p<0.05, ANOVA).
This rise in endothelin production was also significantly
different from the endothelin production at 15 minutes in
the other three groups (p<0.01, ANOVA).
Conclusion: In healthy male volunteers intra-arterial
infusion of AVP induced a rise in endothelin production
in the forearm within 15 minutes, but only after prior infusion of L-NMMA. This observation suggests
that the AVP-induced production of nitric oxide offsets
AVP-mediated release of endothelin.