Early and late changes in endothelial dependent vascular relaxation and contraction responses in the microcirculation of diabetic rats
Year: 2020
Type: dissertation
Abstract: Diabetes is associated with micro and macrovascular complications which \ncontributes to endothelial dysfunction (ED) and leads to cardiovascular diseases. \nED is characterized by impairment of endothelium-dependent relaxation and \nincreases in endothelium-dependent contraction. The endothelial cells release \nfactors that cause endothelial relaxation and contraction. The role of these factors in \nthe microvasculature of diabetes is not well characterized. There were three main \nobjectives of this study; firstly, to determine the contribution of nitric oxide (NO), \nprostacyclin, endothelium-dependent hyperpolarization (EDH) and thromboxane \n(TXA2) receptor in endothelium-dependent relaxation and contraction in the \nmicrocirculation of diabetic rats; secondly, to determine the expression of enzymes \nand receptors involved in mediating endothelial responses and finally to determine \nthe early (2 weeks) and late changes (10 weeks) in the functional and molecular \nresponses in the microcirculation of diabetes rats. This study consisted of four \nexperimental groups; normal 2-week rats, diabetic 2-week rats, normal 10-week \nrats and diabetic 10-week rats (n=15 rats per group). Vascular function studies were \nperformed using wire myography. The contributions of individual EDRF (NO, \nprostacyclin and EDH) and TXA2 receptor in mediating endothelium-dependent \nrelaxations and contractions were evaluated in tail arteries of all the experimental \ngroups. The expressions and distributions of endothelial nitric oxide synthase \n(eNOS), cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2), prostacyclin \nsynthase (PGIS), prostacyclin (IP) receptor, TXA2 receptor and TXA2 synthase \nproteins were determined by Western blotting and immunohistochemistry. \nEndothelium-dependent relaxations were significantly decreased in diabetic 2-week \n[Rmax; 73.49 (11.04) % vs 89.32 (10.03) %, p=0.002] and diabetic 10-week rats \n[Rmax; 58.84 (18.79) % vs 89.32 (10.03) %, p<0.01], respectively compared with \nnormal 2-week rats. NO-mediated relaxations were attenuated in diabetic 10-week \nrats compared with normal 2-week (p<0.001) and normal 10-week rats (p<0.001). \nEDH-mediated relaxations were lower in diabetic 10-week rats compared to normal \n2-week rats (p=0.012) and normal 10-week rats (p=0.017). Diminished relaxations \nto prostacyclin were seen in diabetic 10-week rats compared to normal 2-week \n(p<0.001) and diabetic 2-week rats (p=0.033). Western blotting and \nimmunostaining showed that diabetes reduced expression of eNOS, IP receptor and \nPGIS proteins in rat tail arteries. For endothelium-mediated contractions, significant \nincrease in endothelium-dependent contractions were seen in diabetic 10-week rats \n[Emax; 113.73 (51.32) % vs 34.80 (21.00) %, p<0.001], with a trend of increase in \ndiabetic 2-week rats [Emax; 71.80 (46.02) % vs 34.80 (21.00) %, p<0.058] compared \nto normal 2-week rats. Significant increases in both COX-1 and COX-2 mediated \ncontractions, and TXA2 receptor mediated contractions were seen in diabetic 10- \nweek rats. Trend of increased expression of COX-2 and TXA2 receptor proteins \nwere observed in diabetic 10-week rats supporting the findings of functional \nstudies. In conclusion, impairment in microvascular endothelium-dependent \nrelaxations and increased endothelium-dependent contractions were observed in \ndiabetic rats, and this worsened by prolonged diabetes. Therefore, early prevention \nis necessary to manage ED which may be reversible at an early stage of diabetes.
Author: Seetha Munisamy
Language: English
Subfield: Physiology (medical)
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W3122810158