Acute Effects of Ppar Agonists, Wy14643 and Fenofibrate, on Contractions in Aortae of Aged, Diabetic and Hypertensive Rats

Author:   Hui Chen ,  陈卉
Publisher:   Open Dissertation Press
ISBN:  

9781361041079


Publication Date:   26 January 2017
Format:   Hardback
Availability:   Temporarily unavailable   Availability explained
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Acute Effects of Ppar Agonists, Wy14643 and Fenofibrate, on Contractions in Aortae of Aged, Diabetic and Hypertensive Rats


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This dissertation, Acute Effects of PPAR Agonists, Wy14643 and Fenofibrate, on Contractions in Aortae of Aged, Diabetic and Hypertensive Rats by Hui, Chen, 陈卉, was obtained from The University of Hong Kong (Pokfulam, Hong Kong) and is being sold pursuant to Creative Commons: Attribution 3.0 Hong Kong License. The content of this dissertation has not been altered in any way. We have altered the formatting in order to facilitate the ease of printing and reading of the dissertation. All rights not granted by the above license are retained by the author. Abstract: Endothelial dysfunction is a common characteristic of aging, diabetes and hypertension. It favors the shift towards the production of endothelium-derived contracting factors (EDCF), including prostanoids and reactive oxygen species (ROS), over that of endothelium-derived relaxing factors. The peroxisome proliferator-activated receptor alpha (PPARα) agonists, clinically used as lipid lowering drugs, are reported to have antioxidant properties and beneficial effects in the vascular system. The present study aimed to examine the acute effects of Wy14643 and fenofibate, the PPARα agonists, on endothelium-dependent contractions in aortae of rats with aging, diabetes and hypertension, conditions that are associated with increased oxidative stress.Endothelium-dependent contractions were greater in Wistar-Kyoto rats (WKY) with aging (80 weeks old) and spontaneously hypertensive rats (SHR; 38 to 44 weeks old), than in adult WKY rats (36 to 44 weeks old). They were mediated by cyclooxygenase (COX)-1 and thromboxane-prostaglandin receptor (TP receptor). COX-2, which can be induced by aging, contributed in part to the contraction in aged WKY. The greater contraction may be attributed to increased release of EDCF; which appeared to be different in different conditions. In aged WKY aortae stimulated with calcium ionophore A23187, the COX-derived EDCF was likely to be prostacyclin (PGI2) and superoxide anion whereas in SHR aortae with acetylcholine, it appeared to be hydrogen peroxide and hydroxyl radical. In contrast, the endothelium- and COX-dependent contractions were smaller in streptozotocin (STZ)-induced diabetic than in the age-matched (20 to 21 weeks old) non-diabetic Sprague Dawley rats. The lack of COX-2 involvement in diabetes probably accounts for the impairment.Acute treatment with Wy14643 or fenofibrate significantly reduced endothelium-dependent contractions in aging, diabetes and hypertension; the reduction was due to a decreased release of COX-derived EDCF. Wy14643 and fenofibrate significantly decreased PGI2 production in aged WKY, thereby reducing the contraction; a reduction in superoxide anion generation may also be involved. In SHR aortae, the contraction to hydrogen peroxide, like acetylcholine, was dependent on activation of COX and TP receptor; activation of calcium-independent phospholipase A2 (iPLA2) also played a role. The findings suggest that acetylcholine evoked endothelium-dependent contraction in hypertension via COX-ROS-PLA2-COX signaling. Wy14643 and fenofibrate, through decreasing the activity of iPLA2, attenuated the contraction to hydrogen peroxide; this mechanism may account for their reduction of endothelium-dependent contraction in hypertension. Wy14643 and fenofibrate act in the endothelium to produce the acute inhibition of endothelium-dependent contractions in diabetes and hypertension. Studies examining the involvement of PPAR in this inhibitory effect of Wy14643 did not provide a definite indication, and so further experiments are warranted to identify the direct cellular target for Wy14643 to acutely inhibit the endothelium-dependent contractions. In summary, acute treatment with Wy14643 or fenofibrate reduces endothelium-dependent contractions in aortae of aged, diabetic and hypertensive rats. They produce the inhibitory effect by acting in the endothelium to decrease the production of COX-derived EDC

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Author:   Hui Chen ,  陈卉
Publisher:   Open Dissertation Press
Imprint:   Open Dissertation Press
Dimensions:   Width: 21.60cm , Height: 1.30cm , Length: 27.90cm
Weight:   0.780kg
ISBN:  

9781361041079


ISBN 10:   1361041072
Publication Date:   26 January 2017
Audience:   General/trade ,  General
Format:   Hardback
Publisher's Status:   Active
Availability:   Temporarily unavailable   Availability explained
The supplier advises that this item is temporarily unavailable. It will be ordered for you and placed on backorder. Once it does come back in stock, we will ship it out to you.

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