FAILURE OF AN ENDOTHELIN ANTAGONIST TO MODIFY HYPOPERFUSION AFTER TRANSIENT GLOBAL-ISCHEMIA IN THE RAT

The role of endogenous endothelins in medicating postischaemic hypoper fusion after transient global ischaemia was investigated in halothane- anaesthetised rats. Pretreatment with the broad-spectrum (ET(A) and ET (B)) endothelin antagonist, Bosentan (17 mu mol/kg) had minimal effect on postischaemic hypoperfusion, measured by hydrogen clearance, in th e caudate nucleus and the parietal cortex in the 3 h after bilateral c ommon carotid artery occlusion with concomitant haemorrhagic hypotensi on (transient global ischaemia). In a separate series of rats with CBF measured by [C-14]iodoantipyrine autoradiography at 90 min after caro tid occlusion with concomitant haemorrhagic hypotension, Bosentan trea tment failed to significantly alter CBF in any of the 35 brain regions examined. No significant alterations in CBF, measured by hydrogen cle arance, were observed after transient bilateral common carotid artery occlusion. [C-14]Iodoantipyrine autoradiography at 90 min after occlus ion failed to demonstrate any significant increases in CBF after trans ient bilateral common carotid artery occlusion in any of the 35 brain regions examined in anaesthetised rats. The failure of the broad-spect rum endothelin antagonist Bosentan, at concentrations known to inhibit the cerebrovascular effects of exogenous ET-1, provide no support for the view that endothelins have a major role in mediating acute postis haemic hypoperfusion.