The mechanism of inhibitory actions of propofol on rat supraoptic neurons

Background: In the perioperative period, plasma osmotic pressure, systemic blood pressure, and blood volume often change dramatically. Arginine vasopr essin is a key factor in the regulation of these parameters. This study was performed to evaluate the direct effects and the mechanism of the actions of propofol on arginine vasopressin release from magnocellular neurosecreto ry neurons in the rat supraoptic nucleus. Methods: Somatodendritic arginine vasopressin release from supraoptic nucleus slice preparations was measure d by radioimmunoassay. Ionic currents were measured using the whole-cell mo de of the patch-clamp technique in supraoptic nucleus slice preparations or in single dissociated supraoptic nucleus neurons of the rat. Results: Propofol at concentrations greater than 10(-5) M inhibited the arg inine vasopressin release stimulated by potassium chloride (50 mM). This in hibition by propofol was not reversed by picrotoxin, a gamma-aminobutyric a cid(A) (GABA(A)) receptor antagonist, whereas arginine vasopressin release induced by glutamate (10(-3) M) was also inhibited by propofol at a clinica lly relevant concentration (10(-6) M). The latter effect was reversed by pi crotoxin. Propofol evoked Cl- currents at concentrations ranging 10(-6) to 10(-4) M. Propofol (10(-6) M) enhanced the GABA (10(-6) M)-induced current synergistically. Moreover, propofol (10(-6) M) prolonged the time constant of spontaneous GABA-mediated inhibitory postsynaptic currents. Furthermore, propofol (10(-5) M and 10(-4) M) reversibly inhibited voltage-gated Ca2+ c urrents, whereas it did not affect currents induced by glutamate (10(-3) M) . Conclusions: Propofol inhibits somatodendritic arginine vasopressin release from the supraoptic nucleus, and the enhancement of GABAergic inhibitory s ynaptic inputs and the inhibition of voltage-gated Ca2+ entry are involved in the inhibition of arginine vasopressin release.