Effects of ETB receptor stimulation and its subcellular pathways were evaluated in carbachol pre-contracted rabbit iris sphincter muscles (n=51). ETB stimulation with sarafotoxin (SRTX-c; 10-10-10-6 M) was tested in the absence (n=7) or presence of 10-5 M of: BQ-788 (ETB2 receptor antagonist; n=6), L-NA (NOS inhibitor; n=7) or indomethacin (cyclooxygenase inhibitor; n=10). Effects of ETB stimulation by endothelin-1 (ET-1; 10-10– 10-7 M) in the presence of an ETA receptor antagonist (BQ-123; 10-5 M; n=7) and of ETB1 stimulation by IRL-1620 (10-10–10-7 M; n=7) were also tested. Finally, the effects of SRTX-c (10-9–10-7 M) in electric field stimulation (EFS) contraction were evaluated (n=7). ETB receptor stimulation by SRTX-c or ET-1 in presence of BQ-123 promoted a concentration-dependent relaxation of the rabbit iris sphincter muscle by 10.8±2.0 % and 9.4±1.8 %, respectively. This effect was blocked by BQ-788 (-2.3±2.0 %), L-NA (4.5±2.3 %) or indomethacin (2.3±2.9 %). Selective ETB1 stimulation by IRL-1620 did not relax the iris sphincter muscle (0.9±5.4 %). EFS elicited contraction was not altered by SRTX-c. In conclusion, ETB receptor stimulation relaxes the carbachol precontracted iris sphincter muscle, an effect that is mediated by the ETB2 receptor subtype, through NO and the release of prostaglandins.

Laboratory of Physiology Faculty of Medicine University of Porto Porto

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