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M. E. Kelly, E. Tredger, A. X. Dong, J. N. MacIntyre, S. E. Howlett; Effect of Sex and Age on Contractility of Retinal Arterioles in Rats. Invest. Ophthalmol. Vis. Sci. 2010;51(13):5004.
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Dysregulation of the retinal vasculature is a component of several age-related retinal and optic nerve diseases that result in vision loss including, diabetic retinopathy, glaucoma and macular degeneration. Furthermore, retinal blood flow has been shown to decrease with age in humans and sex differences in vasoconstriction have been observed in a variety of vascular beds. Therefore, we examined the in vitro effects of age and sex on myogenic contractility and endothelial function in isolated retinal arterioles.
Retinal arterioles were isolated from young (3 months) and aged (24 months) Fischer-344 rats of both sexes. Isolated vessel fragments (10 - 35 µm) were placed in an experimental bath on the stage of an inverted microscope and superfused with Ringers composed of (in mM): 145 NaCl, 5 KCl, 10 HEPES, 5 D-Glucose, 2 CaCl2, 1 MgCl2, pH 7.30. Drugs were applied to the isolated vessels via a 6-channel rapid switcher and changes in arteriole diameter were measured using a video edge detector. To examine the endothelial cell function, recordings were made in both endothelium-intact vessels and in vessels denuded of endothelium by perfusion with 0.3% CHAPS.
Endothelin-1 (ET-1) caused prolonged vasoconstriction in isolated arterioles from both young and aged animals. Arteriole constriction induced by 10 nM ET-1 was not significantly different between young females and young males or between young and aged males. However, ET-1 arteriole contractility was significantly decreased in vessels from aged females compared to young females and young males (p<0.001). Removal of the endothelium in vessels from aged females increased ET-1 responsiveness and resulted in ET-1-induced vasoconstriction that was no longer significantly different from that observed in young animals or aged males.
An age-induced decrease in responsiveness to ET-1 in retinal microvasculature was only present in female rats. However, in the absence of functioning endothelium, this effect of age was no longer apparent.
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