DIMINISHED BRAIN SYNAPTIC PLASMA-MEMBRANE CA2-ATPASE ACTIVITY IN SPONTANEOUSLY HYPERTENSIVE RATS - ASSOCIATION WITH REDUCED ANESTHETIC REQUIREMENTS()

We have recently reported that plasma membrane Ca2+-ATPase (PMCA) pump ing activity in rat brain synaptic plasma membranes (SPM) was reduced by in vit ro or prior in vivo exposure to inhalation anesthetics (IA). In addition, rats with streptozocin-induced diabetes were found to ha ve diminished brain synaptic PMCA pumping and a decrease in the partia l pressures of several IA required to prevent movement in response to stimulation, defined as the minimum effective dose or MED. Diminished PMCA activity in erythrocytes of spontaneously hypertensive rats (SHR) has been noted. Because PMCA is ubiquitous, it seemed possible that P MCA pumping might be decreased in the brain of SHR and perhaps associa ted with decreased IA requirement. Eighteen SHR and 18 control, normot ensive Wistar-Kyoto rats (WKY) were studied. PMCA activity was assesse d by measurement of Ca2+ uptake into synaptic plasma membrane vesicles prepared from cerebrum and diencephalon-mesencephalon (D-M) in WKY an d SHR. Ca2+ pumping was significantly less in SHR than in WKY, 85% of control in the cerebrum and 90% in the D-M (p<0.01). The MEDs for halo thane, isoflurane and desflurane were also lower in SHR than in WKY, 9 1%, 90% and 89%, respectively, of control (p<0.05). Thus, an animal mo del of primary hypertension (SHR) manifested diminished brain synaptic PMCA activity and reduced MED for several volatile anesthetics. These findings provide further evidence for a role for PMCA in anesthetic a ction.