Reduced Mechanical Stretch Induces Enhanced Endothelin B Receptor-Mediated Contractility via Activation of Focal Adhesion Kinase and Extracellular Regulated Kinase 1/2 in Cerebral Arteries from Rat.

Cerebral ischaemia results in enhanced endothelin B (ETB ) receptor-mediated contraction and receptor protein expression in the affected cerebrovascular smooth muscle cells (SMC). Organ culture of cerebral arteries is a method to induce similar alterations in ETB receptor expression. We suggest that rapid and sustained reduction in wall tension/stretch is a possible trigger mechanism for this vascular remodelling.

Permanent distal occlusion of middle cerebral artery in rat causes local increased ETB, 5-HT₁B and AT₁ receptor-mediated contractility downstream of occlusion.

Background/aims: In response to experimental stroke, a characteristic functional and expressional upregulation of contractile G-protein-coupled receptors has been uncovered in the affected cerebral vasculature; however, the mechanism initiating this phenomenon remains unknown.

Methods: Using a model of permanent distal occlusion of rat middle cerebral arteries, we investigated whether there was a regional difference in receptor-mediated contractility of segments located upstream and downstream of the occlusion site. The contractile response to endothelin, angiotensin and 5-hydroxytryptamine receptor stimulation was studied by sensitive wire myograph.

Improvement in neurological outcome and abolition of cerebrovascular endothelin B and 5-hydroxytryptamine 1B receptor upregulation through mitogen-activated protein kinase kinase 1/2 inhibition after subarachnoid hemorrhage in rats.

Object: Delayed cerebral ischemia after subarachnoid hemorrhage (SAH) remains a major cause of death and disability. It has been hypothesized that cerebrovascular upregulation of vasoconstrictor receptors is a key step in the development of delayed cerebral ischemia. Upregulation of endothelin-B (ET(B)) and 5-hydroxytryptamine 1B (5-HT(1B)) receptors has been demonstrated in cerebral artery smooth muscles in the delayed ischemic phase after experimental SAH, and intracellular signaling via the mitogen-activated protein kinase kinase (MEK)-extracellular signal-regulated kinase 1/2 pathway has been shown to be involved in this upregulation.