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ROLE OF ANGIOTENSIN CONVERTING ENZYMES ACE AND ACE2 IN DIABETES INDUCED CARDIOVASCULAR DYSFUNCTION

Kanakamedala, Keerthy

Abstract Details

2007, Master of Science (MS), Wright State University, Pharmacology and Toxicology.
Kanakamedala, Keerthy M.S., Department of Pharmacology and Toxicology, Wright State University, 2007. Role of Angiotensin converting enzymes ACE and ACE2 in diabetes induced cardiovascular dysfunction Cardiovascular disease is a long term complication of diabetes, which remains a leading cause of mortality and morbidity. There is recent evidence for activation of the Renin angiotensin system (RAS) in diabetic animals and humans. Emerging evidence shows that the vasoconstrictor actions of Ang II may be opposed by formation of the vasodilator, Ang (1-7). There is limited data on blood pressure in murine models of type 2 diabetes. The aim is to study the role of angiotensin converting enzymes ACE and ACE2 in diabetes induced cardiovascular dysfunction using type 2 diabetic murine mouse models (db/db mice). Both db/db mice and their controls were implanted with carotid telemetric probes for chronic monitoring of MAP (Mean Arterial pressure), heart rate and activity. At 8-9 weeks age, mice showed hyperinsulinemia, hyperglycemia and increase in body weight compared to their lean controls while MAP was not altered. At an older age (14-15 weeks) there was a significantly increased BP in the db/db mice compared to controls. In young (8 weeks) normotensive mice there was a highly significant increase in plasma ACE activity in db/db mice compared to controls. In contrast there was increased ACE2 activity and decreased ACE activity in kidney in 8 weeks old db/db mice compared to controls. No significant difference between ACE and ACE2 activity was observed in lungs and brain. In addition western blot analysis for ACE/ACE2 protein expression also revealed that there was a significant increase in kidney ACE2 and decrease in kidney ACE protein expression in 8 weeks old db/db mice compared to their lean controls. In addition no difference was observed between lung ACE and ACE2 protein expression. Increased plasma and kidney ACE activity and a decreased kidney ACE2 activity were observed in 24 weeks old db/db mice. In conclusion: 1. Eight weeks’ db/db mice were normotensive despite an increase in plasma ACE activity. 2. There was an age dependent increase in the BP but no change in heart rate (HR) in both young and old mice. 3. ACE2 may play a compensatory mechanism against development of hypertension in db/db mice in the early stage of type2 diabetes. 4. The up regulation of ACE coupled with a down regulation of ACE2 might be the cause for hypertension at a later stage in this murine model of type2 diabetes.
Khalid Elased (Advisor)
81 p.

Recommended Citations

Citations

  • Kanakamedala, K. (2007). ROLE OF ANGIOTENSIN CONVERTING ENZYMES ACE AND ACE2 IN DIABETES INDUCED CARDIOVASCULAR DYSFUNCTION [Master's thesis, Wright State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=wright1196272791

    APA Style (7th edition)

  • Kanakamedala, Keerthy. ROLE OF ANGIOTENSIN CONVERTING ENZYMES ACE AND ACE2 IN DIABETES INDUCED CARDIOVASCULAR DYSFUNCTION. 2007. Wright State University, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=wright1196272791.

    MLA Style (8th edition)

  • Kanakamedala, Keerthy. "ROLE OF ANGIOTENSIN CONVERTING ENZYMES ACE AND ACE2 IN DIABETES INDUCED CARDIOVASCULAR DYSFUNCTION." Master's thesis, Wright State University, 2007. http://rave.ohiolink.edu/etdc/view?acc_num=wright1196272791

    Chicago Manual of Style (17th edition)