ON THE PUTATIVE MECHANISTIC BASIS FOR INTRAOPERATIVE PROPOFOL-INDUCEDPENILE ERECTIONS

Propofol is an hypnotic drug used in anesthesia which was noted to ind uce marked vasodilation in vivo and in vitro, and to elicit intraopera tive penile erections. The goal of this study was to assess the putati ve mechanistic basis for this later observation by confirming its acti on in vivo in a rat model of penile erection, as well as by studying i ts effects in vitro on cultured human corporal smooth muscle cells and isolated corporal tissue strips. In vivo experiments were conducted o n Fisher 344 rats anesthetized with sodium pentobarbital or propofol. Intracavernosal pressure was recorded during current stimulation of ca vernous nerves. A significant increase in the intracavernous pressure response was recorded at all levels neurostimulation, ranging from 1-1 0 mA. In vitro experiments were conducted utilizing digital imaging mi croscopy to assess the effects of propofol (3-12 mu g/mL) on ET-l-indu ced (50 nM) intracellular Ca2+ transients [Ca2+](i) in Fura-2-loaded c ultured human corporal smooth muscle cells (passage 3-4) as well as to evaluate the effects of propofol on phenylephrine (PE)induced contrac tile responses on isolated corporal tissue strips. With respect to the former, resting cytosolic calcium levels were not altered during prei ncubation with propofol alone at clinically effective concentrations ( 12 mu g/mL). However, propofol produced a concentration-dependent decr ease in the peak amplitude of the transient ET-l-induced (50 nM) [Ca2](i) response (P < 0.01). Preincubation of the cells with calcium free /EGTA (1mM) buffer produced a reduction in the peak amplitude of the E T-l-induced [Ca2+](i) transient (55.5+/-6% (n=10 cells, P<0.01)) which was indistinguishable from that produced by 8 mu g/mL of propofol (53 .4 +/- 5.6% (n = 12 cells, P < 0.01)). However, propofol had no effect on the histamine-induced [Ca2+](i) response. Lastly, preincubation of isolated human corporal tissue strips with propofol (100-200 mu M; 30 min) caused a significant diminution in the peak amplitude of the PE- induced contractile response. Taken together, these data indicate that the mechanistic basis for intraoperative penile erections observed wi th propofol may be related, at least in part, to altered transmembrane calcium flux through voltage-dependent calcium channels, and thus, de creased corporal smooth muscle tone.