ABSTRACT
The vasoconstrictor responses of isolated rat portal vein and aorta to synthetically prepared endothelin are investigated. Both preparations respond to 10(-9) M levels of the peptide although the aortic response is more sustained than that of the portal vein. Endothelin-evoked contractions, unlike those evoked by scorpion alpha-toxins (which are homologous to endothelin) or by veratridine, are insensitive to tetrodotoxin or to the removal of sodium ions from the tissue-bathing medium. Contractile responses to endothelin may still be observed in high-potassium depolarizing medium and are not dependent on the presence of extracellular chloride; however, the responses are dependent on the presence of extracellular calcium and are blocked by nitrendipine, nifedipine, or nickel. Endothelin-evoked uptake of 45Ca into aortic tissue is also independent of extracellular sodium or potassium and is blocked by nifedipine. These data strongly suggest that endothelin acts at a site closely coupled to the calcium channel and that depolarization by sodium influx through voltage-dependent channels is not involved in endothelin-induced vasoconstriction.
Subject(s)
Aorta/drug effects , Peptides/pharmacology , Portal Vein/drug effects , Animals , Calcium Channels/physiology , Endothelins , Endothelium, Vascular/metabolism , Ions , Male , Models, Cardiovascular , Perfusion , Phenylephrine/pharmacology , Potassium/pharmacology , Rats , Rats, Inbred Strains , Renal Circulation/drug effects , Sodium/pharmacology , VasoconstrictionABSTRACT
The role of sodium and calcium ions in the vasoconstrictor response of isolated rat aorta and protal vein to synthetically prepared endothelin is investigated. Contractile responses to endothelin, unlike those induced by the sodium channel activator veratridine, are unaffected by tetrodotoxin or by the removal of sodium chloride from the solution bathing the tissue. The responses are the same whether sodium chloride is replaced iso-osmotically with either sucrose or potassium chloride. The endothelin responses in all media are entirely dependent on the presence of extracellular calcium, and can be blocked by 1 microM nitrendipine. These findings offer no support to the idea that voltage activated sodium channels are the primary site of action of endothelin as suggested by sequence homologies to scorpion alpha-toxins, but are entirely consistent with the possibility that the site of action of endothelin is closely coupled to the calcium channel (Yanagisawa et al, 1988).
