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Seskoati Prayitnaningsih, Hidayat Sujuti, Mochamad Aris Widodo, Nur Permatasari, Febriani Yohana, Aulia Abdullah Hamid; Activation of ET-1 Signaling Pathway in Central Retinal Artery Induced by Systemic Hypertension. Invest. Ophthalmol. Vis. Sci. 2016;57(12):6006.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: The molecular mechanisms leading to glaucoma caused by hypertension remain unclear. Endothelin-1 (ET-1) as a potent vasoconstrictor can induce an endothelial dysfunction in Central retinal artery (CRA) and also has a potential role in the pathogenesis of Hypertension. This study tested the hypothesis that duration of hypertension affect the activation of ET-1 signaling pathway in CRA, initiated by the imbalance between ET-1 and eNOS
Methods: Experimental study was performed on 20 male Spraque dawley rats that were devided into control group (1), and hypertension groups (2-4). The hypertension was induced by subcutaneous deoxycorticoacetate (DOCA) 10 mg/kg BW twice a week+ NaCl 0.9% daily for 2, 6, and 10 weeks. Blood pressure was measured using animal BP analyzer. Retinal tissue preparations by paraffin blocks were performed after enucleation. The expression of ET-1, eNOS, ET-1 Receptor A (ETRA), ET-1 Receptor B (ETRB), and activation of Myosin Light Chain Kinase (MLCK), and Caldesmon (CaD) in CRA were evaluated through immunofluorescent staining method then observed using laser scanning confocal microscopy. Data were analyzed with one way Anova or Kruskal Wallis Test and Mann Whitney Test.
Results : Blood pressure significantly increased in all of hypertension groups compared to control (p=0.001). ET-1 expression (1238.6±55.1 au) and eNOS activation (2814.2±70.7 au) were found highest in 2 weeks of hypertension, although ratio ET-1/eNOS decreased since 2 week. ETRA reached peak expression in 10 weeks of hypertension (1219.4±6.3 au), while ETRB significantly increased only in 2 weeks group (1069.2±9.6 au). The highest MLCK expression (1190.09±58.32 au), CaD (1670.28±18.36 au) were also found in 2 weeks of hypertension.
Conclusion: The duration of hypertension affect the activation of ET-1 signaling pathway significantly in CRA. The highest value were achieved at 2 weeks, which is the development phase of hypertension.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
The Role of Hypertention on ET-1 activation
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