We have measured the direct effects of propofol 10(-7)-10(-4) mol litre-1 on isolated canine cerebral, coronary, mesenteric, femoral and renal arteries. In arterial strips precontracted submaximally with potassium chloride or prostaglandin F2 alpha (PGF2 alpha), propofol induced further contractions at low concentrations (10(-6)-10(-5) mol litre-1) and relaxation at high concentrations (10(-4) mol litre-1). Intrafat, which contains soya bean oil, egg phosphatide and glycerol in similar concentration to the emulsion formulation of propofol, had a small relaxant effect at a concentration corresponding to propofol 10(-4) mol litre-1. In humans, clinically relevant plasma concentrations of propofol have been reported to be 1-5 x 10(-5) mol litre-1, 97-99% of which is bound to plasma proteins. Therefore, the results obtained in this study demonstrated that clinically relevant concentrations of propofol did not have direct vasodilator effects.

Six new xenicane diterpenes have been isolated from the acetone extract of the soft coral Xenia florida. Two of them are diterpenes containing a bicyclic [4.3.1] ring system. Three of them seem to be precursors for diterpenes possessing the bicyclic [4.3.1] ring system. One is a common monocarbocyclic diterpene with a cyclononane skeleton.

Recently, it has been shown that endoplasmic reticulum (ER) stress causes apoptosis. However, the mechanism of the ER stress-dependent pathway is not fully understood. In human neuroblastoma SH-SY5Y cells, we detected a caspase-12-like protein that has a molecular mass (approximately 60 kDa) similar to that of mouse caspase-12. Thapsigargin, an inhibitor of ER-associated Ca(2+)-ATPase, induced the degradation of caspase-12-like protein. In addition, the degradation of caspases-9 and -3, cleavage of poly(ADP-ribose) polymerase, DNA fragmentation, and cell death were also observed. Pretreatment with phorbol-12-myristate-13-acetate, which induces the expression of antiapoptotic Bcl-2, inhibited thapsigargin-induced degradation of caspases-9 and -3, but not caspase-12-like protein degradation. A caspase inhibitor, benzyloxycarbonyl-Val-Ala-Asp(OCH(3))-CH(2)F, inhibited the degradation of caspase-12-like protein, but not that of caspases-9 and -3. These results suggest that thapsigargin may induce the activation of both ER- and mitochondria-dependent pathways in human SH-SY5Y cells.

The findings that sevoflurane suppressed the effects of arachidonic acid, but not those of prostaglandin G2 and STA2, suggest strongly that sevoflurane inhibited TXA2 formation by suppressing cyclooxygenase activity. Halothane appeared to suppress both TXA2 formation and binding to its receptors. Sevoflurane has strong antiaggregatory effects at subanesthetic concentrations (greater than 0.13 mM; i.e., approximately 0.5 vol/%), whereas halothane has similar effects at somewhat greater anesthetic concentrations (0.49 mM; i.e., approximately 0.54 vol/%). Isoflurane at clinical concentration (0.84 mM; i.e., approximately 1.82 vol/%) does not affect platelet aggregation significantly.

Volatile anaesthetics inhibit endothelium-dependent relaxation, but the underlying mechanism(s) have not been clarified. In an attempt to elucidate the mechanism(s), we determined the effects of halothane, isoflurane and sevoflurane on relaxation induced by acetylcholine and sodium nitroprusside (SNP) and the cGMP formation elicited by exogenous nitric oxide (NO) and SNP in rat aortas. Acetylcholine (10(-7)-10(-5) M)-induced relaxation was attenuated by halothane (2%), isoflurane (2%) and sevoflurane (4%). SNP (10(-8) M)-induced relaxation was reduced by halothane (2%), but not by isoflurane (2%) or sevoflurane (4%). The cGMP level of NO-stimulated aorta was reduced by halothane (2%) and sevoflurane (4%), but not by isoflurane (2%). The cGMP level of SNP (10(-7) M)-stimulated aorta was reduced by halothane (2%), but not by isoflurane (2%) and sevoflurane (4%). We conclude that the mechanisms responsible for the inhibition of endothelium-dependent relaxation differ among anaesthetics. Isoflurane inhibits the relaxation mainly by inhibiting the formation of NO in the endothelium. In contrast, the effect of halothane on endothelium-dependent relaxation may be largely due to the inhibition of action of NO in the vascular smooth muscle and the effect of sevoflurane may be to inactivate NO or to inhibit the action of NO.