ET-1- and NO-mediated signal transduction pathway in human brain capillary endothelial cells

Abstract

mobilization in these cells is dose-dependently inhibited by NOR-1 (an NO donor). This inhibition was prevented by ODQ (an inhibitor of guanylyl cyclase) or Rp-8-CPT-cGMPS (an inhibitor of protein kinase G). Treatment of endothelial cells with 8-bromo-cGMP reduced ET-1-induced Ca 2ϩ mobilization in a manner similar to that observed with NOR-1 treatment. In addition, NOR-1 or cGMP reduced Ca 2ϩ mobilization induced by mastoparan (an activator of G protein), inositol 1,4,5-trisphosphate, or thapsigargin (an inhibitor of Ca 2ϩ -ATPase). Interestingly, alterations in endothelial cytoskeleton (actin and vimentin) were associated with these effects. The data indicate for the first time that the cGMP-dependent protein kinase colocalizes with actin. These changes were accompanied by altered levels of phosphorylated vasodilator-stimulated phosphoprotein, which were elevated in endothelial cells incubated with NOR-1 and significantly reduced by ODQ or Rp-8-CPTcGMPS. The findings indicate a potential mechanism by which the functional interrelationship between ET-1 and NO plays a role in regulating capillary tone, microcirculation, and blood-brain barrier function. capillary endothelium; endothelin-1; nitric oxide; calcium mobilization; cytoskeleton THE CENTRAL MICROCIRCULATORY BED (composed of small arteries, capillaries, and venules) is the main intermediary structure responsible for maintaining the cellular homeostasis in the brain. Its regulatory functions principally reside within the endothelium, which consists of a single layer of flat cells. In microvessels, the endothelium forms a continuous inner lining, whereas in the capillaries it provides a single cellular barrier between the blood and brain. These endothelial cells (EC) express a variety of biological activities, including the control of vascular tone and blood flow through the Address for reprint requests and other correspondence: R. M. McCarron,

Cytocompatibility of electrospun nanofiber tubular scaffolds for small diameter tissue engineering blood vessels

“…Also, SDRAEC on the scaffolds could be investigated by its characteristic markers for phenotypic expression. Factor VIII was a typical endothelial cell marker which was usually used for evaluation the phenotype of endothelial cell on scaffolds [43]. According to our observations, electrospun pNSR32/PCL/Gt scaffolds, did not influence expression of factor VIII antigen associated with SDRAECs, which preliminarily exhibited that pNSR32/PCL/Gt scaffolds can not only contribute to a greater density of cells but also maintain the function of SDRAECs.…”

Cerebral autoregulation is temporarily disturbed in the early recovery phase after dynamic resistance exercise

“…This indicates an increased pulsatility of CBFV, although CVR was dramatically reduced and Vm still remained at the exercise level in this phase. These conflicting results from the CVR and PI calculation have been reported previously, particularly in various presyncopal and syncopal situations [5,12,25,35,38] and might reflect a fast reduction in CVR mainly in the upstream vessels due to a fast release of vasodilating substances like nitric oxide or adenosine [6,31] in order to counterbalance a sudden drop in BP, while the peripheral vessels downstream still produce a relatively high resistance. However, despite its rapid decline, BP (and HR) never dropped below normal resting values during recovery in our tests.…”

Cocaine- and Amphetamine-Regulated Transcript (CART) Peptide: A Vasoactive Role in the Cerebral Circulation

“…It has recently been posited that endothelin and NO contribute interrelated vasoconstrictor and vasodilator effects in the regulation of tone within the cerebral microcirculation (Chen et al, 2003). The potential involvement of the endothelin system, specifically the ET B receptor, and its relationship to the NO system in the regulation of cerebral blood flow deserves further study.…”