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- W2330736756 abstract "Background: Synchronization of cellular activity is essential for cardiovascular function, such as the heart beat or vasocontractility. This is achieved through gap junctions and their constituent connexin (Cx) proteins. When Cx40, which highly expressed in the heart, juxtaglomerular apparatus and vascular endothelium, is globally deleted or mutated, significant cardiovascular pathology is observed in both animals and humans. However, the precise function of Cx40 in these different tissues remains unknown. We therefore aimed to determine the impact on cardiovascular function of endothelially expressed Cx40. Methods: We generated transgenic mice in which Cx40 function in the vascular endothelium was reduced through expression of a mutant form, ΔCx40, under control of the endothelium specific promoter, Tie2. We assessed active and passive properties of small mesenteric arteries by measuring the myogenic response to intraluminal pressure and determining vascular elasticity. The involvement of nitric oxide and endothelium derived hyperpolarising factor (EDHF) was determined pharmacologically, while blood pressure and renin secretion were also measured. Results: The myogenic response of mesenteric arteries from ΔCx40 mice was activated at significantly lower intraluminal pressures than in wildtype mice (EC50: Wildtype, 41.7± 0.3mmHg, n=13; ΔCx40, 33.2±0.4 mmHg, n=13; P<0.001). This occurred due to loss of contribution from EDHF. Transgenic vessels also exhibited reduced distensibility (P<0.05) without hypertrophic remodelling of the vascular wall. A modest but significant increase in blood pressure was observed in these mice without change in renin secretion. Conclusions: Life-long impairment in endothelial Cx40 enhances vasoconstriction, reduces vasodilator capacity and arterial distensibility and elevates blood pressure." @default.
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- W2330736756 date "2012-09-01" @default.
- W2330736756 modified "2023-10-17" @default.
- W2330736756 title "260 CHRONIC IMPAIRMENT OF ENDOTHELIAL CONNEXIN40 ENHANCES ARTERIAL CONSTRICTION AND REDUCES ARTERIAL DISTENSIBILITY" @default.
- W2330736756 doi "https://doi.org/10.1097/01.hjh.0000420155.78636.33" @default.
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