Human endothelin subtype A receptor enhancement during tissue culture via de novo transcription.
OBJECTIVE
Endothelin (ET) has, since its discovery, increasingly been considered a key player in the pathophysiological processes of cerebral vasospasm in the course of subarachnoid hemorrhage, although it remains unclear how ET is involved. We present data that indicate an inherent capacity of human cerebral arteries to change their sensitivity to ET.


METHODS
Human cerebral arteries were obtained from patients undergoing intracranial tumor surgery. The vessels were divided into segments and subjected to organ culture for 48 hours. The vessels were then examined by using in vitro pharmacological methods and molecular biological techniques.


RESULTS
After organ culture of the cerebral arteries, both the sensitivity to and potency of ET were enhanced (maximal response, 152 +/- 9%; -log (50% effective concentration), 10.3 +/- 0.3), in comparison with data for fresh cerebral arteries. Contractions were inhibited by both FR139317 (a specific ET(A) receptor antagonist) and bosentan (a mixed ET(A) and ET(B) receptor antagonist), in a manner indicating the sole presence of contractile ET(A) receptors. An inconsistent dilative response to the selective ET(B) receptor agonist sarafotoxin 6c was observed; the response was preserved in some segments and abolished in others, and potentiation of the precontraction was observed in yet other segments. No isolated contractile response to sarafotoxin 6c was observed, however. In reverse transcription-polymerase chain reaction assays, both ET(A) and ET(B) receptor messenger ribonucleic acid was detected.


CONCLUSIONS
These results demonstrate that human cerebral arteries are capable of enhancing the function of ET(A) receptors.
Hansen-Schwartz
Jacob
J
Department of Clinical Experimental Research, Glostrup Hospital, DK-2600 Glostrup, Denmark. jacob.schwartz@dadlnet.dk
Nordström
Carl-Henrik
CH
Edvinsson
Lars
L
D002536:Cerebral Arteries / Q000473:pathology*; D046508:Culture Techniques; D019332:Endothelin-1 / Q000502:physiology; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic; D020301:Vasospasm, Intracranial / Q000235:genetics / Q000473:pathology
D019332:Endothelin-1; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin