Cerebral vasoconstriction after subarachnoid hemorrhage - Role of changes in vascular receptor phenotype

The pathological constriction of cerebral arteries known as cerebral vasospasm (CVS) is with a delay of 4 to 10 days linked to subarachnoid hemorrhage. Several agents have been suggested as being responsible; amongst these perhaps 5-hydroxytryptamine (5-HT) and endothelin-1 (ET-1) are the most prominent given their ability to elicit powerful constriction of cerebral arteries. Investigating both 5-HT and ET receptors we have observed that there are distinct changes in receptor phenotype after experimental SAH, namely upregulation of the ETB and 5-HT1B receptors, and that this upregulation is linked to a higher sensitivity to the endogenous agonists. It has also been shown that reduction in regional cerebral blood flow (CBF) is associated with receptor upregulation and interventional animal experiments have shown a benefit from inhibiting the PKC and MAP kinase pathways on receptor upregulation, CBF and neurological outcome.