Pharmacology of endothelins: vascular preparations for studying ETA and ETB receptors

Three rabbit vessels, the carotid and pulmonary arteries and the jugular vein were investigated to identify vascular monoreceptor systems (either ET_A or ET_B) to be used in structure-activity studies on endothelins and their antagonists. The RbCA has been found to behave as a monoreceptor ETA preparation, since it shows much greater sensitivity to ET-1 than to ET-3 and is insensitive to IRL 1620. The contractile response of the RbCA to ET-1 is reduced in the presence of BQ-123 but is not influenced by BQ-788. The RbPA behaves as a pure ET_B system when stimulated with the ET_B selective agonist IRL 1620. The contractile effect of IRL 1620 is reduced in the presence of BQ-788 but is not influenced by BQ-123. The RbJV responds to ET_A and to IRL 1620 with contractions that are reduced by both BQ-123 and BQ-788, respectively. The RbJV appears to be a mixed ET_A and ET_B system in which the two functional sites play an equivalent role in the stimulatory contractile response.Thus, contractile ET_A and ET_B receptors have been found in arterial and venous vessels of the rabbit and some of these vessels provide sensitive and selective (either ET_A or ET_B) preparations that appear to be adequate for pharmacological studies on ET receptor agonists or antagonists.