J Korean Neurosurg Soc.  1998 Aug;27(8):1015-1022.

Pressor Effect of Intracerebroventricular 4-Aminopyridine on the Systemic Arterial Pressure in the Rabbit

• Lim JS
• Kang SY
• Baik YH
• Kang SS

Abstract

A K+-channel blocker, 4-aminopyridine(4-AP) increases neurotransmitter release from motor nerve terminals and has been shown to restore neuromuscular transmission in the myasthenic syndrome. It has been reported that the intravenous injection of 4-AP in the myasthenic patients caused many central adverse effects including anxiety and restlessness, but did not affect the blood pressure. The aim of this study was to observe the effect of intracerebroventricularly administered 4-AP on the blood pressure and to elucidate the mechanism of the action in urethane-anesthetized rabbits. Intracerebroventricular(icv) 4-AP produced pressor effects in a dose-dependent fashion, but intravenous(iv) 4-AP of the same dose did not altered the blood pressure. Tetraethylammonium, a K+-channel blocker which differs from 4-AP structurally, had little effect on the blood pressure, but 3,4-diaminopyridine, another derivative of the aminopyridine, produced pressor effect similar to 4-AP. The pressor effect of icv 4-AP was not affected by the treatment with iv phenoxybenzamine and chlorisondamine, and in bilateral adrenalectomized rabbits. These results suggest that the 4-AP pressor effect is not related to the periphral sympathetic nerve nor adrenal gland. The pretreatment with icv phentolamine and prazosin did not altered the 4-AP pressor. However, the icv 4-AP pressor effect was significantly attenuated by the treatment with icv yohimbine, and significantly potentiated by the treatment with icv clonidine. The treatment with icv diltiazem markedly inhibited the icv 4-AP pressor effect. It is concluded that 4-AP-sensitive K+-channels in rabbit brain might play a role in the regulation of blood pressure and that the 4-AP pressor effect is closely related to the central alpha2-adrenoceptors and L-type calcium channels.

Keyword

K+-channel blocker; 4-aminopyridine; Urethane-anesthetized rabbit; Intracerebroventricular; Pressor effect; alpha-adrenoceptors

MeSH Terms

4-Aminopyridine*
Adrenal Glands
Anxiety
Arterial Pressure*
Blood Pressure
Brain
Calcium Channels, L-Type
Chlorisondamine
Clonidine
Diltiazem
Humans
Injections, Intravenous
Neurotransmitter Agents
Phenoxybenzamine
Phentolamine
Prazosin
Psychomotor Agitation
Rabbits
Tetraethylammonium
Yohimbine
4-Aminopyridine
Calcium Channels, L-Type
Chlorisondamine
Clonidine
Diltiazem
Neurotransmitter Agents
Phenoxybenzamine
Phentolamine
Prazosin
Tetraethylammonium
Yohimbine