|M.Sc Student||Amsalem Mazal|
|Subject||Oxidative Stress and Inflammation in Sabra Hypertensive|
Rats (SBH/y) and Resistant Rats (SBN/y)
|Department||Department of Medicine||Supervisors||Ms. Batya Kristal|
|Assistant Professor Shifra Sela|
Oxidative stress (OS) and inflammation are among the mechanisms causing endothelial dysfunction underlying atherosclerosis in hypertension. In our previous work and in other experimental models, hypertension was accompanied by primed peripheral polymorphonuclear leukocytes (PMNLs) inducing systemic OS and inflammation, however the causative relationship between OS and hypertension was not evaluated.
Aims: To investigate the connection between OS and inflammation and hypertension.
Methods: Sabra salt sensitive hypertension prone rats (SBH) and resistant (SBN), maintained for 4 weeks on deoxycorticosterone acetate (DOCA) and 1% salt in their drinking water (DOCA/salt) were compared to their untreated counterpart controls. OS was assessed by the rate of superoxide (O2-) release from PMNLs, plasma levels of oxidized (GSSG) and reduced glutathione (GSH), malondialdehyde (MDA) and plasma carbonylated fibrinogen. Plasma fibrinogen levels, PMNLs number and their ex-vivo viability reflected inflammation.
Results: Untreated SBN and SBH were normotensive, while DOCA/salt induced severe hypertension in SBH but not in SBN. Both untreated and treated SBH groups showed increased: O2- release, carbonylated fibrinogen, GSSG, MDA and PMNLs number compared to SBN. These parameters were further exacerbated in the treated SBH.
Conclusion: Primed PMNLs may be a contributing factor to several pathogenetic features of the hypertension syndrome. The presence of OS and inflammation in normotensive but genetically hypertension prone SBH rats, suggests causative interrelationship, as they precede hypertension. The exacerbation of OS inflammation in hypertensive SBH may be consequential to high blood pressure or contribute to it. Thus, these SBH are exposed to three independent risk factors to develop atherosclerosis: hypertension, OS and inflammation. This study established OS and inflammation phenotype in a salt sensitive genetic model of hypertension.