The effect of arginine vasopressin on endothelin production in the human forearm vascular bed.
OBJECTIVE
To study whether arginine vasopressin (AVP) can stimulate endothelin production and/or release in vivo, in the human forearm vasculature.


METHODS
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-NG-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).


CONCLUSIONS
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.
Postma
C T
CT
Department of Internal Medicine, Division of General Internal Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. c.postma@aig.umcn.nl
Maessen
S M J
SM
Thien
Th
T
Smits
P
P
D000328:Adult; D001127:Arginine Vasopressin / Q000008:administration & dosage / Q000494:pharmacology*; D016022:Case-Control Studies; D016232:Endothelins / Q000096:biosynthesis* / Q000097:blood; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D005542:Forearm / Q000098:blood supply*; D006801:Humans; D007261:Infusions, Intra-Arterial; D008297:Male; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D012039:Regional Blood Flow; D013997:Time Factors; D014662:Vasoconstrictor Agents / Q000008:administration & dosage / Q000494:pharmacology*; D019323:omega-N-Methylarginine / Q000008:administration & dosage / Q000494:pharmacology
D016232:Endothelins; D004791:Enzyme Inhibitors; D014662:Vasoconstrictor Agents; D001127:Arginine Vasopressin; D019323:omega-N-Methylarginine; D019001:Nitric Oxide Synthase