Repeatability of local forearm vasoconstriction to endothelin‐1 measured by venous occlusion plethysmography

Aims  We  investigated  the  repeatability  of  the  forearm  blood  flow  response  to intra-arterial infusion of endothelin-1 (ET-1), assessed by venous occlusion ­plethysmography. Methods In eight healthy men (aged 18–50 years), on four separate occasions, ET-1 (2.5 or 10 pmol min−1) was infused for 120 min via a 27 SWG cannula sited in the brachial artery of the nondominant arm. Each dose level was administered twice on consecutive visits. The dose order was randomized. Results are expressed as percentage change from baseline at 120 min (mean ± s.e. mean). Results ET-1 caused significant vasoconstriction (P < 0.0001 anova) at both doses (38 ± 3%, 2.5 pmol min−1 and 62 ± 3%, 10 pmol min−1; mean visit 1 and 2). There was no difference in the response to either dose on repeated challenge. Responses appeared to be less variable when expressed as percentage change in the ratio of blood flow (infused:noninfused) in both arms than as percentage change in blood flow in the infused arm alone, as indicated by repeatability coefficients (15% vs 21%, 2.5 pmol min−1 and 11% vs 13%, 10 pmol min−1; ratio vs infused arm alone). Conclusions We have shown dose-dependent vasoconstriction in the forearm vascular bed to intra-arterial infusion of ET-1 and that this response is less variable when expressed as percentage change in the ratio of forearm blood flow than percentage change in the infused arm. These data should also provide useful information to determine the power of early clinical pharmacology studies investigating the activity of endothelin receptor antagonists.