Vasoconstrictor actions of endothelin-1 in human resistance vessels.
The contractile response to endothelin-1 was studied in isolated human resistance vessels in the presence and absence of extracellular calcium. Endothelin-1 was 1000-fold more potent than noradrenaline, with an ED50 of 6.5 +/- 1.26 x 10(-9) mol/l compared with 2.1 +/- 0.7 x 10(-6) mol/l. Calcium depletion by repeated stimulation with noradrenaline in a calcium-free medium attenuated but did not prevent a sustained contraction in response to endothelin-1 (30% of control). On re-adding calcium to the bath a full contraction immediately occurred. These experiments suggest that an endothelin-1-induced contraction is largely dependent on the presence of extracellular calcium, but a partial contraction can be induced in a calcium-free medium and this may be dependent on mobilization of intracellular calcium from a store not affected by repeated noradrenaline stimulation.
Watt
P A
PA
Department of Medicine, Leicester Royal Infirmary, UK.
Baker
A R
AR
Thurston
H
H
D000328:Adult; D000368:Aged; D004305:Dose-Response Relationship, Drug; D016232:Endothelins; D004730:Endothelium, Vascular / Q000502:physiology*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology*; D014655:Vascular Resistance / Q000187:drug effects*; D014661:Vasoconstriction / Q000187:drug effects*
D016232:Endothelins; D010455:Peptides; D009638:Norepinephrine