The actions of endothelins-1 and -3 on the vascular and capsular smooth muscle of the isolated blood perfused spleen of the dog.

1. Endothelin-1 (ET-1), endothelin-3 (ET-3) and noradrenaline (NA) were administered as intra-arterial bolus injections into the isolated, blood-perfused spleen of the dog to assess agonist properties and relative molar potencies on the vascular and capsular smooth muscle. 2. An initial small vasodilatation was observed occasionally at low doses (1.0-10 pmol) of ET-1. 3. ET-1, ET-3 and NA all caused graded increases in splenic arterial vascular resistance. The molar ED50 for the splenic vasoconstrictor response to ET-1 was significantly less (P less than 0.001) than that to ET-3; both peptides were significantly more potent as vasoconstrictor agents than NA. The maximum increase in splenic arterial vascular resistance was not significantly different for either ET-1, ET-3 or NA. 4. The time course of the splenic vasoconstrictor response to ET-1 was significantly (P less than 0.01) longer than that to equieffective doses of ET-3 or NA. 5. The splenic vasoconstrictor responses to ET-1 and ET-3 were accompanied by reductions in spleen volume. The rank order of molar potency in causing splenic capsular contraction was ET-1 greater than ET-3 greater than NA. The maximum reduction in splenic volume was significantly greater for NA than for either ET-1 or ET-3. The two peptides (ET-1, ET-3) were equiefficacious in contracting splenic capsular smooth muscle. 6. The high molar potency of ET-1 as a splenic arterial vasoconstrictor, over 1,700 times more potent than NA, suggests that it may play an important local role in the control of splenic haemodynamics.