Halothane-induced alteration in the fluidity of rat brain synaptosomal membranes and its relationship to anesthesia.

Concentrations of halothane 1.43% or higher abolished the pain response and induced anesthesia. Halothane increased membrane fluidity of synaptosomes and microsomes both at non-anesthetic and anesthetic concentrations. Changes in fluidity in synaptosomes did not return to control levels even after the animals recovered from anesthesia. Alteration in membrane fluidity by halothane is a non-selective effect and may not play a definitive role in anesthesia.

Halothane and isoflurane alter phospholipid transmethylation in rat brain synaptosomes.

The mechanism of action of inhalational anesthetics is unknown, but neuronal membrane alteration is a favored hypothesis. Since phospholipid methylation and translocation play a key role in the transmission of biologic signals across cell membranes, we examined the effect of two commonly used halogenated anesthetics, halothane and isoflurane, on phospholipid methylation in rat brain synaptosomes. Using S-adenosyl-L-[3H-methyl]methionine as a donor, we found a two-fold increase in 3H-methyl incorporation into phospholipids in synaptosomes taken from rats exposed to concentrations that just abolish pain response, but not in rats exposed to higher or lower concentrations. Methylation was not increased in rats newly recovered from anesthesia. Halothane added to synaptosomes taken from rats not previously exposed to anesthetics stimulated 3H-methyl incorporation over a wide range of concentrations. Enhancement of phospholipid methylation by halothane and isoflurane may effect an alteration of neural signal transduction that results in the anesthetic state.

Dithiothreitol-induced alterations of blood pressure, vascular reactivity and aortic microsomal calcium uptake in spontaneously hypertensive rats.

Dithiothreitol, a potent sulfhydryl reducing agent, depressed systolic blood pressure to a greater extent in genetically hypertensive rats (SHR) than in normotensive Wistar-Kyoto rats (WKY). Dithiothreitol depressed the contractile response to norepinephrine and potassium chloride of isolated aortic strips from both SHR and WKY. Dithio-bis-2-nitrobenzoid acid, a sulfhydryl oxidizing agent, restored the responsiveness of rat aortic strips to these contractile agents. Microsomes isolated from rat aortae sequester calcium in the presence of ATP. This activity, generally referred to as calcium-pump activity, has been postulated to function in smooth muscle relaxation, and is significantly depressed in aortic microsomes of the SHR. Dithiothreitol (10 mM) greatly increased and dithio-bis-2-nitrobenzoic acid (100 micrometer) decreased the ATP-dependent calcium pump activity of microsomes isolated from both SHR and WKY aortae. These observations indicate that sulfhydryl groups may influence systems involved in vascular reactivity and blood pressure regulation.