The mechanism of action of endothelin-1 on small pulmonary arterial vessels.
The effect of endothelin-1, a recently isolated vasoconstrictor peptide, was studied in preparations of pulmonary arterial vessels from the rat. Contraction was measured in large (1-2 mm diameter) and small (150-350 microns diameter) vessels on a Mulvany-Halpern myograph. Endothelin-1 was found to be one of the most potent vasoconstrictors yet described in these isolated pulmonary vessels. The contraction elicited was dose dependent, of slow onset, and prolonged. There was significant difference in sensitivity between the two vessel types, with an EC50 of 8.9 nM for the artery, and 33.1 nM for the smaller vessels. The endothelin-1 stimulated contraction was predominantly dependent on extracellular [Ca2+]. However 34.7% of the contraction in the pulmonary artery and 18.5% in the resistance vessel could be obtained in Ca2+ free (EGTA containing) solution. This extracellular Ca2+ independent fraction was sensitive to depletion of intracellular stores by pretreatment with caffeine or noradrenaline in the artery but not the arteriole. The extracellular Ca2+ dependent fraction was not affected by Ca2+ channel blockade with dihydropydridines or verapamil, but was inhibited by application of cadmium or lanthanum. The contraction was not altered by inhibition of Na+/H+ exchange.
Leach
R M
RM
Department of Medicine, United Medical School, London.
Twort
C H
CH
Cameron
I R
IR
Ward
J P
JP
D000818:Animals; D001160:Arterioles / Q000187:drug effects; D002118:Calcium / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002352:Carrier Proteins / Q000037:antagonists & inhibitors; D016232:Endothelins / Q000494:pharmacology*; D008168:Lung / Q000098:blood supply*; D008297:Male; D011651:Pulmonary Artery / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D017923:Sodium-Hydrogen Exchangers; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects
D002121:Calcium Channel Blockers; D002352:Carrier Proteins; D016232:Endothelins; D017923:Sodium-Hydrogen Exchangers; D014662:Vasoconstrictor Agents; D002118:Calcium