Central effects of paraoxon on haemodynamics in the cat.

Abstract

Application of paraoxon into the left vertebral artery (8--80 micrograms) or both the left and right vertebral artery (4--8 micrograms) of the anaesthetized cat evoked dose-dependent depressor effects, whereas heart rate was not influenced significantly. Also after systemic administration of paraoxon (150--825 micrograms . kg-1), while peripheral muscarinic receptors were blocked, depressor effects were still observed. Dose-response curves for the depressor response to paraoxon were established. Infusion of low doses of dexetimide via the vertebral artery prevented the hypotensive action of paraoxon. The distribution of this antimuscarinic drug in the brain was investigated. The depressor effect of paraoxon can be attributed to both a decrease in peripheral resistance and cardiac output. Decerebration and midcollicular transection were carried out in order to elucidate the site and mechanism of action. The depressor effect of paraoxon seems to be mediated by a central mechanism of action located within the lower brain stem. It is concluded that stimulation of muscarinic receptors in the pontomedullary region gives rise to the observed changes in haemodynamic parameters. Muscarinic receptors in the hypothalamus seem to be of minor importance for the hypotensive action of paraoxon.