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

Abstract

1. The effects of intravenous administration of endothelin (ET) receptor antagonists SB-209670 (0.001-10.0 mg kg(-1)), SB-217242, SB-234551 (0.01-10.0 mg kg(-1)) and BQ-788 (0.001-1.0 mg kg(-1)) were investigated on trigeminal nerve ganglion stimulation-induced neurovascular reflexes in the carotid vasculature of the anaesthetized cat. Comparisons were made with sumatriptan (0.003-3.0 mg kg(-1)) and alpha-CGRP8-37 (0.001-0.1 mg kg(-1)). 2. Trigeminal nerve ganglion stimulation produced frequency related increases 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 reductions in carotid vascular resistance was observed at 10 Hz, and this frequency was selected to investigate the effects of drugs on trigeminal nerve ganglion stimulation-induced responses in guanethidine treated cats. 3. Saline, alpha-CGRP8-37 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 (max. 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 inhibition of trigeminal nerve ganglion stimulation-induced reductions in carotid vascular resistance. Saline, SB-234551, alpha-CGRP8-37 and sumatriptan had no effect. 5. These data demonstrate ET(B) receptor blockade attenuates the vasodilator effects of trigeminal nerve ganglion stimulation in the carotid vascular bed of guanethidine pretreated anaesthetized cats.

• Authors: P Raval, S Bingham, N Aiyar, J D Elliott, A J Hunter, E H Ohlstein, A A Parsons
• Journal: British journal of pharmacology (Br J Pharmacol) Vol. 126 Issue 2 Pg. 485-93 (Jan 1999) ISSN: 0007-1188 [Print] England
• PMID: 10077242 (Publication Type: Journal Article)

Chemical References

• Antihypertensive Agents
• Carboxylic Acids
• Dioxoles
• Endothelin Receptor Antagonists
• Indans
• Oligopeptides
• Peptide Fragments
• Piperidines
• Pyrazoles
• Receptor, Endothelin A
• Receptor, Endothelin B
• Receptors, Endothelin
• SB 234551
• Sympatholytics
• 1H-Indene-2-carboxylic acid, 1-(1,3-benzodioxol-5-yl)-3-(2- (carboxymethoxy)-4-methoxyphenyl)-2,3-dihydro-5-propoxy-, (1S,2R,3S)-
• calcitonin gene-related peptide (8-37)
• BQ 788
• Calcitonin Gene-Related Peptide
• enrasentan
• Guanethidine

Topics

• Anesthesia
• Animals
• Antihypertensive Agents (pharmacology)
• Blood Flow Velocity (drug effects)
• Blood Pressure (drug effects)
• Calcitonin Gene-Related Peptide (pharmacology)
• Carboxylic Acids (pharmacology)
• Carotid Arteries (drug effects, physiology)
• Cats
• Dioxoles (pharmacology)
• Electric Stimulation
• Endothelin Receptor Antagonists
• Guanethidine (pharmacology)
• Heart Rate (drug effects)
• Hemodynamics (drug effects)
• Indans (pharmacology)
• Male
• Oligopeptides (pharmacology)
• Peptide Fragments (pharmacology)
• Piperidines (pharmacology)
• Pyrazoles (pharmacology)
• Receptor, Endothelin A
• Receptor, Endothelin B
• Receptors, Endothelin (physiology)
• Reflex (drug effects, physiology)
• Sympatholytics (pharmacology)
• Time Factors
• Trigeminal Ganglion (drug effects, physiology)
• Trigeminal Nerve (drug effects, physiology)
• Vascular Resistance (drug effects)
• Vasodilation (drug effects)