Key result
Intra-arterial infusion of endothelin-1 caused significant, dose-dependent forearm vasoconstriction (38% at 2.5 pmol/min and 62% at 10 pmol/min; P<0.0001) with good repeatability.
Why the study?
Does intra-arterial infusion of endothelin-1 produce a repeatable dose-dependent vasoconstriction in the forearm vascular bed of healthy men?
RCT (n=8)
Randomized
Does intra-arterial infusion of endothelin-1 produce a repeatable dose-dependent vasoconstriction in the forearm vascular bed of healthy men?
p-value: p=<0.0001
Intra-arterial infusion of endothelin-1 produces a repeatable, dose-dependent vasoconstriction in the forearm vascular bed, which is less variable when expressed as a ratio of infused to noninfused arm blood flow.
Validates endothelin-1 forearm infusion as a repeatable vasoconstriction model in healthy men; supports research use but leaves clinical translation open.
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.
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Strachan et al. (2002) conducted an RCT in Healthy volunteers (n=8). Endothelin-1 (ET-1) vs. Baseline was evaluated on Percentage change from baseline in forearm blood flow at 120 min (p=<0.0001). Intra-arterial infusion of endothelin-1 caused significant, dose-dependent forearm vasoconstriction (38% at 2.5 pmol/min and 62% at 10 pmol/min; P<0.0001) with good repeatability.
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