Trigeminal nerve ganglion stimulation-induced neurovascular reflexes in the anaesthetized cat: Role of endothelin(B) receptors in carotid vasodilatation

1 The effects of intravenous administration of endothelin (ET) receptor ant agonists SB-209670 (0.001 - 10.0 mg kg(-1)), SB-217242, SB-234551 (0.01 - 1 0.0 mg kg(-1)) and BQ-788 (0.001 - 1.0 mg kg(-1)) were investigated on trig eminal nerve ganglion stimulation-induced neurovascular reflexes in the car otid vasculature of the anaesthetized cat. Comparisons were made with sumat riptan (0.003 - 3.0 mg kg(-1)) and alpha-CGRP(8-37) (0.001 - 0.1 mg kg(-1)) . 2 Trigeminal nerve ganglion stimulation produced frequency related increase s in carotid blood flow, reductions in carotid vascular resistance and non- frequency related increases in blood pressure. Guanethidine (3 mg kg(-1), i .v.) blocked trigeminal nerve ganglion-induced increases in blood pressure but had no effect on changes in carotid flow or resistance. Maximal reducti ons in carotid vascular resistance was observed at 10 Hz, and this frequenc y was selected to investigate the effects of drugs on trigeminal nerve gang lion stimulation-induced responses in guanethidine treated cats. 3 Saline, alpha-CGRP(8-37) SB-209670 and BQ-788 had little or no effect on resting haemodynamic parameters. SB-217242 (10 mg kg(-1), n = 3) produced a 56% reduction in arterial blood pressure whereas SB-233451 (10 mg kg(-1), n = 3) produced a 30% reduction in carotid vascular resistance. Sumatriptan produced dose-related reductions in resting carotid flow and increases (ma x. 104% at 0.3 mg kg(-1), n = 5) in vascular resistance. 4 SB-209670 (n = 6 - 7), SB-217242 (n = 3) and BQ-788 (n = 3) produced inhi bition of trigeminal nerve ganglion stimulation-induced reductions in carot id vascular resistance. Saline, SB-234551, alpha-CGRP(8-37) and sumatriptan had no effect. 5 These data demonstrate ETB receptor blockade attenuates the vasodilator e ffects of trigeminal nerve ganglion stimulation in the carotid vascular bed of guanethidine pretreated anaesthetized cats.