Delayed loss of ETB receptor-mediated vasorelaxation after cold lesion of the rat parietal cortex

The aim of this study was to investigate the involvement of endothelins (ET ) in brain injury. The effect of ET was studied in the isolated basilar art ery (BA) taken from control, sham-operated, and cold-lesioned rats. Cold le sion was induced by application of a precooled (-78 degrees C) copper cylin der (outer diameter 5 mm) for 60 seconds to the intact dura over the pariet al cortex. After precontraction with prostaglandin (PG) F-2 alpha, ET-3 (10 (-10) to 10(-8) mol/L) dilated BA with a pD(2) (negative log of the half-ma ximal concentration) of 9.06 +/- 0.031 (mean +/- SD) and a maximal effect ( E-max) of 1.64 +/- 1.0 mN at 3 x 10(-9) mol/L in sham-operated animals. Thi s dilation was reduced 24 and 48 hours after cold lesion by 33% and 73%, re spectively, at 3 x 10-9 mol/L. The effects of acetylcholine (10(-8) to 10(- 4) mol/L) and sodium nitroprusside (10(-3) mol/L) were unaltered. Activatio n of the ETB receptor in thoracic aorta by the specific agonist IRL, 1620 a lso resulted in a reduced dilation (51% by 48 hours after cold lesion). Rev erse transcriptase-polymerase chain reaction of the BA showed unaltered exp ression of mRNA for the ETB receptor after cold lesion whereas ETB immunore activity in BA and in its intraparenchymal arteries was reduced at 24 and 4 8 hours. In contrast to the reduction of ET-3-induced dilation, the constri ctor effects of ET-1 and ET-3 were retained after cold lesion. Endothelin-1 (10(-12) to 10(-6) mol/L) dose-dependently contracted segments of untreate d control BA segments under resting conditions with a pD(2) of 8.03 +/- 0.2 2 and an E-max of 6.35 +/- 0.70 mN. Further evidence that the constrictor a bility of BA was not influenced by cold lesion is given by the unaltered re sponse to 124 mmol/L KC and 10(-6) mol/L serotonin. We conclude that the ET B receptor of BA after cold lesion is downregulated specifically, apparentl y at the posttranscriptional level. Because the ETB-mediated dilation in th oracic aorta was also reduced, downregulation of the ETB receptor apparentl y is not restricted to cerebral arteries. The nitric oxide-cyclic guanosine monophosphate system in BA is, however, intact.