PHARMACOLOGY OF ENDOTHELINS - VASCULAR PREPARATIONS FOR STUDYING ET(A) AND ET(B) RECEPTORS

Three rabbit vessels, the carotid and pulmonary arteries and the jugul ar vein were investigated to identify vascular monoreceptor systems (e ither ET(A) or ET(B)) to be used in structure-activity studies on endo thelins and their antagonists. The RbCA has been found to behave as a monoreceptor ET(A) preparation, since it shows much greater sensitivit y 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 contrac tile effect of IRL 1620 is reduced in the presence of BQ-788 but is no t influenced by BQ-123. The RbJV responds to ET-1 and to RL 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 tw o functional sites play an equivalent role in the stimulatory contract ile response. Thus, contractile ET(A) and ET(B) receptors have been fo und in arterial and venous vessels of the rabbit and some of these ves sels provide sensitive and selective (either ET(A) or ET(B)) preparati ons that appear to be adequate for pharmacological studies on ET recep tor agonists or antagonists.