Functional ETA-ETB Receptor Cross-talk in Basilar Artery In Situ From ETB Receptor Deficient Rats

Yoon, Seonghun; Gariepy, Cheryl E.; Yanagisawa, Masashi; Zuccarello, Mario; Rapoport, Robert M.

doi:10.1097/fjc.0000000000000335

Cited by 3 publications

(2 citation statements)

References 16 publications

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“…(ii) It is a consequence of an altered expressional profile of ET B receptors in the vascular wall from endothelial‐specific expression to VSMC‐specific expression (see figs and S1). (iii) ET B has been shown to dimerize with ET A in VSMCs of cerebral arteries . The VSMC‐specific ET B receptor might dimerize with ET A receptors in the cerebrovascular SMCs and thereby mediate the increased contraction to S6c.…”

Section: Discussionmentioning

confidence: 98%

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

Spray

Rasmussen

Skovsted

et al. 2016

Basic Clin Pharma Tox

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Cerebral ischaemia results in enhanced endothelin B (ET B ) 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 ET B receptor expression. We suggest that rapid and sustained reduction in wall tension/stretch is a possible trigger mechanism for this vascular remodelling. Isolated rat middle cerebral artery (MCA) segments were incubated in a wire myograph with or without mechanical stretch, prior to assessment of their contractile response to the selective ET B receptor agonist sarafotoxin 6c. The involvement of extracellular regulated kinase (ERK) 1/2 and focal adhesion kinase (FAK) was studied by their specific inhibitors U0126 and PF-228, respectively. Compared with their stretched counterparts, unstretched MCA segments showed a significantly increased ET B receptor-mediated contractile response after 12 hr of incubation, which was attenuated by either U0126 or PF-228. The functionally increased ET B -mediated contractility could be attributed to two different mechanisms: (i) a difference in ET B receptor localization from primarily endothelial expression to SMC expression and (ii) an increased calcium sensitivity of the SMCs due to an increased expression of the calcium channel transient receptor potential canonical 1. Collectively, our results present a possible mechanism linking lack of vessel wall stretch/tension to changes in ET B receptormediated contractility via triggering of an early mechanosensitive signalling pathway involving ERK1/2 and FAK signalling. A mechanism likely to be an initiating factor for the increased ET B receptor-mediated contractility found after cerebral ischaemia.In physiological conditions, the powerful vasoconstrictor endothelin 1 (ET-1) induces arterial vasoconstriction primarily via activation of the endothelin A (ET A ) receptor on the vascular smooth muscle cells (VSMCs). During pathological conditions with disturbed blood flow or altered perfusion pressure, a characteristic shift in arterial contractility emerges with arterial segments displaying a considerable contractile response to the stimulation of the otherwise primarily vasodilating endothelin B (ET B ) receptor. Hence, increased ET B receptor-mediated contractions and receptor protein levels have been observed in coronary, mesenteric and middle cerebral arteries (MCAs) affected by disturbed blood flow after ischaemia-reperfusion of the heart and gut, experimental subarachnoid haemorrhage (SAH) and focal ischaemia-reperfusion [1][2][3][4]. Interestingly, a strikingly similar shift in the reactive profile has been observed when subjecting isolated arterial segments to organ culture, a condition which largely mimics conditions of no flow/no perfusion pressure [5][6][7][8][9]. Therefore, organ culture of isolated arterial segments is often used as a method to study phenotypic changes in arterial receptors expression and the mechanisms behind this phenomenon [10].I...

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Section: Discussionmentioning

confidence: 98%

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

Spray

Rasmussen

Skovsted

et al. 2016

Basic Clin Pharma Tox

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“…Thus, the possibility that ET-1-induced non-activated HSC contraction is partly mediated via ET B receptors could not be ruled out, although the selective ET B receptor antagonist BQ-788 had no effect on the contraction. ET A and ET B receptor cross-talk has been shown to occur in ET-1-induced vascular contraction, which might explain the limited efficacy of selective ET A or ET B receptor antagonists compared to non-selective ET receptor antagonists [ 26 , 27 ].…”

Section: Discussionmentioning

confidence: 99%

Quantitative real-time measurement of endothelin-1-induced contraction in single non-activated hepatic stellate cells

et al. 2021

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Although quiescent hepatic stellate cells (HSCs) have been suggested to regulate hepatic blood flow, there is no direct evidence that quiescent HSCs display contractile abilities. Here, we developed a new method to quantitatively measure the contraction of single isolated HSCs and evaluated whether endothelin-1 (ET-1) induced contraction of HSCs in a non-activated state. HSCs isolated from mice were seeded on collagen gel containing fluorescent beads. The beads around a single HSC were observed gravitating toward the cell upon contraction. By recording the movement of each bead by fluorescent microscopy, the real-time contraction of HSCs was quantitatively evaluated. ET-1 induced a slow contraction of non-activated HSCs, which was inhibited by the non-muscle myosin II inhibitor blebbistatin, the calmodulin inhibitor W-7, and the ETA receptor antagonist ambrisentan. ET-1-induced contraction was also largely reduced in Ca2+-free conditions, but sustained contraction still remained. The tonic contraction was further diminished by the Rho-kinase inhibitor H-1152. The mRNA expression of P/Q-type voltage-dependent Ca2+ channels (VDCC), as well as STIM and Orai, constituents of store-operated channels (SOCs), was observed in mouse non-activated HSCs. ET-1-induced contraction was not affected by amlodipine, a VDCC blocker, whereas it was partly reduced by Gd3+ and amiloride, non-selective cation channel blockers. However, neither YM-58483 nor SKF-96365, which inhibit SOCs, had any effects on the contraction. These results suggest that ET-1 leads to Ca2+-influx through cation channels other than SOCs and produces myosin II-mediated contraction of non-activated HSCs via ETA receptors, as well as via mechanisms involving Ca2+-calmodulin and Rho kinase.

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Endothelin-1

Houde

Desbiens

D’Orléans-Juste

2016

Advances in Pharmacology

100

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Functional ETA-ETB Receptor Cross-talk in Basilar Artery In Situ From ETB Receptor Deficient Rats

Cited by 3 publications

References 16 publications

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

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

Quantitative real-time measurement of endothelin-1-induced contraction in single non-activated hepatic stellate cells

Endothelin-1

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