The effect of adrenergic compounds on neurogenic dural vasodilatation.

Abstract

The pharmacology of neurogenic trigeminovascular vasodilator responses in the dura mater is of interest for understanding the pathophysiology of migraine and to develop new therapies for this disabling common condition. Aminergic mechanisms have been implicated in migraine through direct study of amines in patients, and by inference from the pharmacology of many effective anti-migraine compounds, particularly preventative agents. This study used intravital microscopy to assess the role of aminergic transmission in neurogenic dural vasodilatation (NDV) by measuring directly the diameter of dural arteries in sodium pentobarbitone anaesthetised rats. Electrical stimulation of a closed cranial window produces, by local depolarisation of nerves, dural vessel dilation that is monitored continuously on-line using video-microscopy and a video dimension analyser. This dural vasodilatation was not affected by pre-treatment with an alpha1-adrenoceptor agonist (phenylephrine, 1 and 5 microg/kg), or antagonist (corynanthine, 1 and 2 mg/kg), nor by an alpha2-adrenoceptor agonist (UK14,304, 5 microg/kg) or antagonist (yohimbine, 1 and 3 mg/kg). Similarly, we saw no effect of beta-adrenoceptor blockade (propranolol, 1 and 3 mg/kg). The lack of an inhibitory effect of UK14,304 the model of neurogenic dural vasodilation contrasts with its effect in neurogenic dural plasma protein extravasation model. The lack of inhibition of beta-adrenoceptor antagonists in the neurogenic vasodilatation model contrasts with their usefulness as migraine prophylactics, and suggests that their mechanism of action in migraine is unlikely to be through sensory trigeminal fibre terminals at the neurovascular junction. Moreover, the data indicate that the adrenergic system does not play a significant role in neurogenic dural vasodilation.

• Authors: S Akerman, D J Williamson, R G Hill, P J Goadsby
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 424 Issue 1 Pg. 53-8 (Jul 13 2001) ISSN: 0014-2999 [Print] Netherlands
• PMID: 11470260 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adrenergic Agents
• Adrenergic alpha-1 Receptor Agonists
• Adrenergic alpha-1 Receptor Antagonists
• Adrenergic alpha-2 Receptor Agonists
• Adrenergic alpha-2 Receptor Antagonists
• Adrenergic alpha-Agonists
• Adrenergic alpha-Antagonists
• Adrenergic beta-Antagonists
• Quinoxalines
• Phenylephrine
• Yohimbine
• Brimonidine Tartrate
• Propranolol

Topics

• Adrenergic Agents (pharmacology)
• Adrenergic alpha-1 Receptor Agonists
• Adrenergic alpha-1 Receptor Antagonists
• Adrenergic alpha-2 Receptor Agonists
• Adrenergic alpha-2 Receptor Antagonists
• Adrenergic alpha-Agonists (pharmacology)
• Adrenergic alpha-Antagonists (pharmacology)
• Adrenergic beta-Antagonists (pharmacology)
• Animals
• Blood Pressure (drug effects)
• Blood Vessels (drug effects, physiology)
• Brimonidine Tartrate
• Dose-Response Relationship, Drug
• Dura Mater (blood supply, drug effects, physiology)
• Electric Stimulation
• Injections, Intravenous
• Male
• Phenylephrine (pharmacology)
• Propranolol (pharmacology)
• Quinoxalines (pharmacology)
• Rats
• Rats, Sprague-Dawley
• Time Factors
• Vasodilation (drug effects)
• Yohimbine (pharmacology)