Activation of sodium channels is not essential for endothelin induced vasoconstriction.

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).