Methylglyoxal (MG), a metabolite of glucose, causes non-enzymatic glycation of proteins to form irreversible advanced glycation end products (AGEs). Increased MG production, which in turn gives rise to AGEs, has been linked to the development of complications in diabetes. However, the role of MG and AGEs in hypertension has not been investigated widely. The previous study from our laboratory showed that the cellular levels of MG and MG-induced AGE formation are significantly higher in cultured aortic smooth muscle cells from spontaneously hypertensive rats (SHR) than those from normotensive Wistar-Kyoto rats (WKY). Using immunofluorescence staining with specific monoclonal antibodies against MG-induced AGEs, the present studies show a strong association of MG and its AGE products (Nå-carboxyethyl-lysine and Nå-carboxymethyl-lysine) with hypertension in SHR. The blood pressure of SHR was not different from that of WKY rats at 5 wks of age. From 8 wks onwards, blood pressure was significantly elevated compared to age-matched WKY rats. Importantly, this increase in blood pressure coincided with an elevated MG level in plasma and aorta of SHR in an age-dependent fashion compared to age-matched WKY rats, although no difference was observed in blood glucose levels between these two strains. Our data showed an increased MG level in plasma and aorta, but not in kidney or heart, in SHR at an early age of 8 wks, suggesting, in addition to diabetes/hyperglycemic or hyperlipidemic conditions, the accumulation of MG in blood vessel walls plays an important role in the development of hypertension or its complications even in the absence of diabetes. Moreover, we observed increased blood pressure and vascular remodeling in Sprague Dawley rats which had been treated to increase endogenous MG and related AGEs. After inhibiting MG and MG-induced AGE generation in SHR, hypertension development in this genetic hypertension model was delayed and vascular remodeling was reversed. Our data indicate that increased MG and AGE formation may play an important role in the development of hypertension.
| Identifer | oai:union.ndltd.org:USASK/oai:usask.ca:etd-12132007-230430 |
| Date | 14 December 2007 |
| Creators | Wang, Xiaoxia |
| Contributors | Tuchek, John M., Hiebert, Linda M., Hickie, Robert A., Desai, Kaushik, deBlois, Denis, Wu, Lily, Yu, Peter H. |
| Publisher | University of Saskatchewan |
| Source Sets | University of Saskatchewan Library |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://library.usask.ca/theses/available/etd-12132007-230430/ |
| Rights | unrestricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to University of Saskatchewan or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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