Skip to Main Content
 

Global Search Box

 
 
 

ETD Abstract Container

Abstract Header

The Role of Nitric Oxide/Peroxynitrite Imbalance in Diabetes and Salt-Induced Hypertension

Awad, Salah Alsanussi Mousa

Abstract Details

2013, Doctor of Philosophy (PhD), Ohio University, Chemistry and Biochemistry (Arts and Sciences).
Both diabetes and hypertension are risk factors for cardiovascular diseases. Diabetes mellitus and high blood pressure complications are associated with dysfunctional endothelium, where the molecular mechanism is still unclear. Endothelial dysfunction refers to the loss of nitric oxide (NO). The objective of this research was to study the molecular mechanisms of NO, peroxynitrite (ONOO-) (using electrochemical nanosensors) and L-arginine transport in type 2 diabetes and salt-induced hypertension in human umbilical vein endothelial cells (HUVECs). The influence of various concentrations of glucose, sodium chloride (NaCl), sodium (Na+) and chloride (Cl-) on NO, ONOO- release and L-arginine transport was measured in human endothelial cells. Exposure of HUVECs to elevated concentrations of glucose, NaCl, Na+ and Cl- reduced significantly NO release and increased nitroxidative stress levels (elevated ONOO-). L-arginine transport was significantly inhibited under hyperglycemic and hypertensive conditions. NO bioavailability ameliorated under physiological and elevated glucose and salt concentration after the administration of L-arginine. In contrast, ONOO- concentrations decreased significantly after the supplementation of L-arginine. Similar study on African American HUVECs was performed to elucidate the influence of glucose and salt on NO, ONOO- and L-arginine transport. This study showed a decrease in NO and L-arginine transport and an increase in oxidative stress under elevated glucose and NaCl levels. African American HUVECs also produced a lower NO concentration and higher ONOO- level than White American HUVECs. A low ratio of NO to ONOO- [NO]/[ONOO-] in HUVECs under hyperglycemic and hypertensive conditions clearly imply a dysfunctional endothelium. Similarly, the effect of glucose on NO, ONOO-, L-arginine transport and insulin secretion was studied in hamster pancreatic beta cells (HIT-T15) under various glucose concentrations. Elevated glucose concentrations reduced significantly NO, L-arginine transport and insulin release from hamster beta cells. In contrast, ONOO- release increased significantly. Endothelial nitric oxide synthase (eNOS) expression in hamster beta cells was reduced after 2 and 4 hours incubation with high glucose. Elevated glucose and sodium chloride concentrations also activate NADPH oxidase enzyme and increase the synthesis of superoxide anion (O2-), which reacts with NO and forms cytotoxic ONOO-. Treatment of HUVECs and hamster beta cells with NADPH oxidase inhibitor increased NO bioavailability and reduced significantly ONOO- release. However, restoration of NO bioavailability and reduction of the oxidative/nitroxidative stress in impaired endothelial cells was observed at elevated L-arginine concentration in the presence of NADPH oxidase inhibitor. This study is the first to show fundamental molecular events leading to diabetes and salt-induced hypertension.
Tadeusz Malinski, Dr. (Advisor)
192 p.

Recommended Citations

Citations

  • Awad, S. A. M. (2013). The Role of Nitric Oxide/Peroxynitrite Imbalance in Diabetes and Salt-Induced Hypertension [Doctoral dissertation, Ohio University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1375119568

    APA Style (7th edition)

  • Awad, Salah. The Role of Nitric Oxide/Peroxynitrite Imbalance in Diabetes and Salt-Induced Hypertension. 2013. Ohio University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1375119568.

    MLA Style (8th edition)

  • Awad, Salah. "The Role of Nitric Oxide/Peroxynitrite Imbalance in Diabetes and Salt-Induced Hypertension." Doctoral dissertation, Ohio University, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1375119568

    Chicago Manual of Style (17th edition)