Permanent Distal Occlusion of Middle Cerebral Artery in Rat Causes Local Increased ET_B, 5-HT_1B and AT₁ Receptor-Mediated Contractility Downstream of Occlusion

Abstract

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. Results: Only downstream segments exhibited an augmented contractile response to stimulation with each of the three ligands, with the response towards sarafotoxin 6c being especially augmented compared to sham, upstream and contralateral controls. This functional increase did not seem to relate to ischemic tissue damage, inflammatory cell infiltration or the element of reperfusion. Interestingly, immunohistochemistry did not show any difference in the level of immunoreactivity towards endothelin B (ET_B) receptors between groups. Conclusion: Single artery occlusion without significant visible infarct resulted in locally increased ET_B, angiotensin type 1 and 5-hydroxytryptamine 1B receptor-mediated contractile responses only in segments located downstream of the occlusion site. This suggests lack of wall stress as an initiating trigger leading to regulation of contractile response after cerebral stroke.

Protein nitration impairs the myogenic tone of rat middle cerebral arteries in both ischemic and nonischemic hemispheres after ischemic stroke

“…Experimental studies have provided us with this opportunity to address this question and to compare the vascular responses in the nonischemic hemisphere with sham controls. Rasmussen et al (33) showed that permanent distal occlusion of the MCA increased the contractile response to angiotensin, endothelin, and 5-HT in segments downstream of the occlusion. We (5) have previously shown that ACh-induced maximum relaxation was reduced in basilar arteries isolated from rats subjected to MCAO.…”

Enhancing cerebral perfusion with external counterpulsation after ischaemic stroke: how long does it last?

“…In clinical studies, reduced cerebral blood flow has been reported in the non-ischaemic as well as ischaemic hemisphere after stroke, and if this impairment of blood flow in the non-ischaemic hemisphere is prolonged, it may affect the stroke severity and recovery 33 34. Experimental studies have shown that permanent distal occlusion of the MCA in rat brain increased the contractile response to angiotensin, endothelin and 5-hydroxytryptamine in segments downstream of the occlusion 35. Previously, Coucha et al 36 reported that acetylcholine-induced maximum relaxation was reduced in basilar arteries isolated from rats subjected to MCA occlusion.…”

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

“…Tissue was maintained in ice‐cold PSS during dissection of vessel segments. In a recent study using a model of focal permanent distal MCA occlusion, where the ligation was placed near the bifurcation of the MCA, an increased ET B receptor‐mediated response was reported . Therefore, for the sake of comparison in the current study, vessel segments (2 mm) were carefully dissected out just prior to and after the first branch point of the MCA (denoted main part and branch, respectively).…”

“…A recent in vivo study in our laboratory using an experimental permanent MCA occlusion method showed that ET B receptor‐mediated contractile responses were solely observed in arterial segments located downstream to the occlusion site, meaning that it did not seem to be related to the element of reperfusion but rather the actual lack of flow/tension . In organ culture, arterial segments are removed from their native tissue, and thereby, the luminal flow and mechanical forces acting on the vascular wall in vivo are removed.…”

“…Together, these results lead us to suggest that changes in mechanical stress brought about by altered hemodynamic forces is the initial trigger for organ culture‐induced up‐regulation of ET B receptor‐mediated contractility. This was investigated by culturing isolated MCA segments corresponding to the segments used in the permanent MCA occlusion model with or without mechanical stretch using a wire myograph, combined with protein determination and localization studies.…”