MEK1/2 mediated transcriptional upregulation of contractile receptors, including endothelin-1 (ET-1) receptors, has previously been shown to be a factor in the pathology of SAH.
In both regimens, trametinib treatment caused significant reductions in the endothelin-1 induced contractility after SAH, which is believed to be associated with endothelin B receptor up-regulation.
ET-1 (endothelin-1) and its receptors have been implicated in the pathophysiology of large artery spasms after SAH; however, their role in the development of microvascular dysfunction is currently unknown.
The synthesis of ET-1 is enhanced after subarachnoid hemorrhage (SAH) to mediate a long-lasting vasoconstriction, and PGF2a contributes to cerebral inflammation and vasoconstriction.
The present study aimed to investigate the expression of ET‑1 in cerebrospinal fluid (CSF) in patients with SAH and to analyze rat arterial contractility and the expression levels of ET‑1 receptors in vitro.
There is evidence that endothelin-1 may contribute to the pathophysiology of conditions associated with sustained vasoconstriction, such as hypertension and heart failure, vasospastic conditions, such as subarachnoid hemorrhage, and atherogenesis.
There is now also a wealth of evidence suggesting that endothelin-1 is a key mediator in a range of cardiovascular diseases associated with sustained vasoconstriction, such as chronic heart failure, and with vasospasm, such as subarachnoid haemorrhage.