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Big endothelin‐3 constricts forearm resistance vessels but not hand veins in humans
Author(s) -
Ferro Charles J.,
Strachan Fiona E.,
Shepherd Ewan,
Haynes William G.,
Webb David J.
Publication year - 2000
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1067/mcp.2000.107523
Subject(s) - forearm , vasoconstriction , plethysmograph , medicine , dorsum , vein , constriction , vascular resistance , hemodynamics , endothelin 1 , anatomy , anesthesia , receptor
Background Endothelin‐3 (ET‐3) and its inactive precursor, big endothelin‐3 (big ET‐3), are both found in human plasma. We investigated whether big ET‐3 is converted to ET‐3 in the human forearm resistance vessels and dorsal hand veins in vivo. Methods In a 4‐phase study, 6 subjects received 90 minute intrabrachial artery infusions of big ET‐3 (50 and 100 pmol · min −1 ) and ET‐3 (5 and 10 pmol · min −1 ) in random order. Forearm blood flow was measured by venous occlusion plethysmography. In a second 3‐phase study, 6 subjects received 90‐minute dorsal hand vein infusions of saline solution, big ET‐3 (50 pmol · min −1 ) and ET‐3 (5 pmol · min −1 ) in random order. In a third 2‐phase study, 6 subjects received 90‐minute dorsal hand vein infusions of big ET‐3 (100 pmol · min −1 ) and ET‐3 (10 pmol · min −1 ). In the dorsal hand vein studies, vessel diameter was measured by the Aellig technique. Results Intra‐arterial ET‐3 caused local forearm vasoconstriction of 20% ± 9% ( P = .009) at 5 pmol · min −1 and 20% ± 10% ( P = .001) at 10 pmol · min −1 after 90 minutes, with no difference between doses ( P = .69). Intra‐arterial big ET‐3 also caused local forearm vasoconstriction of 22% ± 6% at 50 pmol · min −1 ( P = .004) and 18% ± 3% at 100 pmol · min −1 ( P < .0001) after 90 minutes, with no difference between doses ( P = .44). There were no significant differences between the responses to intra‐arterial big ET‐3 and ET‐3 at these doses. Local intravenous ET‐3 caused a constriction of 9% ± 2% at 5 pmol · min −1 ( P = .04) and 22% ± 8% at 10 pmol · min −1 ( P = .002) after 90 minutes. Big ET‐3 at 50 pmol · min −1 and 100 pmol · min −1 did not affect hand vein tone. All responses were slowly progressive. Conclusions Based on vasoconstriction, measurable conversion of big ET‐3 to ET‐3 occurs in forearm resistance vessels but not in dorsal hand veins in vivo. An endothelin‐converting enzyme, capable of converting exogenously administered big ET‐3 to ET‐3, appears to be present in upper limb resistance arteries but not in capacitance vessels in humans. Clinical Pharmacology & Therapeutics (2000) 68 , 67–74; doi: 10.1067/mcp.2000.107523