The effects of endothelin-1 on isolated bovine ciliary muscles.

The effects of endothelin-1 on bovine ciliary muscle were investigated in vitro using muscle strips prepared in two different directions (longitudinal and circular). Fifty-two bovine ciliary muscle strips (4 x 6 mm) were prepared. Chemicals were added to both types of strips suspended in an organ chamber, and their changes in isometric tension were recorded. The concentration-response relationship of endothelin-1 (n = 20), the magnitudes of contractions caused by endothelin-1 and carbachol (n = 12), and the effects of an endothelin receptor subtype A antagonist BQ123 (n = 4) and an endothelin receptor subtype B agonist IRL1620 (n = 4) were studied. The cumulative addition of endothelin-1 caused relaxation at low concentrations (10(-11) and 10(-10) M), while it caused contraction of the ciliary muscles at high concentrations (10(-9), 10(-8) and 3 x 10(-8) M). The magnitude of the contraction caused by 10(-8) M endothelin-1 was about 30% in the longitudinal muscle strips and 29% in the circular muscle strips, relative to the contraction caused by 10(-5) M carbachol, a muscarinic agonist. The contractile response caused by 10(-8) M endothelin-1 was abolished and converted to relaxation by pretreatment with BQ123, a selective endothelin receptor subtype A antagonist. Single addition of IRL1620, a selective endothelin receptor subtype B agonist, caused only relaxation. These results suggest that, endothelin-1 causes not only contraction at high concentrations, but also relaxation at low concentrations in bovine ciliary muscle. Also, it suggested that the relaxation is mediated by endothelin receptor subtype B, whereas the contraction is mediated by endothelin receptor subtype A.