Big endothelin-3 constricts forearm resistance vessels but not hand veins in humans

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 E T-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 ar tery infusions of big ET-3 (50 and 100 pmol . min(-1)) and ET-3 (5 and 10 p mol . min(-1)) in random order. Forearm blood flow was measured by venous o cclusion 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 st udy, 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 s tudies, 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). Int ra-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 1.44).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% 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 t o ET-3 occurs in forearm resistance vessels but not in dorsal hand veins in vivo. An endothelin-converting enzyme, capable of converting exogenously a dministered big ET-3 to ET-3, appears to be present in upper limb resistanc e arteries but not in capacitance vessels in humans.