Date of Award
2019
Document Type
Open Access Master's Thesis
Degree Name
Master of Science in Kinesiology (MS)
Administrative Home Department
Department of Kinesiology and Integrative Physiology
Advisor 1
Zhiying Shan
Committee Member 1
Jason Carter
Committee Member 2
Qinghui Chen
Committee Member 3
Feng Zhao
Abstract
Orexin is a neuropeptide with a large range of functions, with a recently discovered role in blood pressure (BP) regulation. Although the role of brain orexin system in hypertension has been investigated in several hypertensive animals, it remains unclear whether activation of the orexin system contributes to the development of Deoxycorticosterone-acetate (DOCA) hypertension, an animal model of human salt sensitive hypertension. In this study, we investigated the hypothesis that Orexin-1 receptor (OX1R) expression is increased in the paraventricular nucleus (PVN), a critical brain area controlling cardiovascular function, which subsequently increases vasopressin (AVP) expression and peripheral secretion, resulting in hypertension development in this model. Seven to eight-week-old male Sprague Dawley (SD) rats were split into three groups including DOCA-salt, untreated controls, and OX1RshRNA-DOCA rats. Following knockdown of OX1R in the PVN via viral infection in the OX1RshRNA-DOCA rats, they, as well as the DOCA-salt group, were implanted with a 75mg DOCA pellet and treated with 1%NaCl/0.2%KCl drinking water, while the control group remained untreated. Blood pressure of each rat was measured using tail-cuff plethysmography. Three weeks following DOCA-salt or sham treatment, all rats were sacrificed, and brains were subjected to either real-time PCR or immunostaining to assay mRNA level and protein expression of Orexin A, OX1R, and AVP in the PVN. Their blood was collected for plasma AVP measurement, and their hearts were weighed for measurement of their heart weight/body weight (BW/HW) ratio. Our results showed that chronic knockdown of the PVN OX1R effectively attenuated hypertension induced by DOCA-salt treatment (control: 107.91±5.99 vs. DOCA-salt: 142.43±7.73 vs. DOCA+OX1RshRNA: 115.69±8.23 mmHg; P
Recommended Citation
Bigalke, Jeremy, "THE OREXIN SYSTEM IN DOCA-SALT HYPERTENSION: REGULATION OF VASOPRESSIN", Open Access Master's Thesis, Michigan Technological University, 2019.