Richard Reichl

Inhibition of neurosympathetic cerebroarterial constriction by clonidine in cats

In cats anaesthetized with chloralose the cervical sympathetic nerves were separated from the vagosympathetic trunk and severed. Bilateral preganglionic electrical stimulation of the efferent sympathetic stumps induced rate-dependent decrements in cerebrospinal fluid pressure measured in the cerebral lateral ventricle. Intravenous injection of 3, 10, and 30 micrograms/kg clonidine caused a dose-related shift in threshold and inhibition of the pressure decrease particularly at lower rates of stimulation. Intravenous infusion of 3.75 micrograms/kg . min yohimbine for 30 min reduced the inhibitory effect of 30 micrograms/kg clonidine i.v. Intravenous injection of 5 mg/kg phentolamine reduced the depressor effect at all rates of electrical sympathetic stimulation. In another group of cats craniotomy was performed and the diameter of pial arteries (0.1-0.2 mm) was measured with an eyepiece micrometer under the microscope. Bilateral electrical stimulation of the sympathetic nerves decreased the artery diameter by 16%. This effect was diminished by 30 micrograms/kg clonidine i.v. Because of the characteristic shift of the frequency-response curve caused by clonidine and the antagonistic effect of yohimbine it is assumed that clonidine inhibits sympathetic neurotransmission in pial arteries by activation of prejunctional alpha-adrenoceptors. The inhibitory effect of clonidine in neurosympathetic transmission might explain the efficacy of the drug in the treatment of migraine.