Date of Award

2016

Document Type

Open Access Master's Thesis

Degree Name

Master of Science in Biological Sciences (MS)

Administrative Home Department

Department of Biological Sciences

Advisor 1

Zhiying Shan

Committee Member 1

Qing-Hui Chen

Committee Member 2

Feng Zhao

Abstract

Elevated plasma arginine vasopressin (AVP) levels have been found in human hypertension subjects and several salt dependent experimental animal models of hypertension including the Dahl salt sensitive hypertension (SSHTN) model. The orexin system is involved in AVP regulation and its over activation has been implicated in hypertension, however, the role of brain orexin in SSHTN is unknown. We hypothesized that increased activity of orexin in the paraventricular nucleus (PVN), a prominent region in AVP production, contributes to SSHTN via enhancing AVP signaling. Eight-week-old male adult Dahl salt sensitive (DS) and age and sex matched Sprague Dawley (SD) rats were placed on either a high salt (HS, 8% NaCl) or normal salt (NS, 0.4% NaCl) diet for 5 weeks. Five weeks HS intake did not increase mean arterial pressure (MAP) or alter PVN mRNA expression of chronic neuronal activation marker Fra1, orexin receptor 1 (OX1R), or orexin receptor 2 (OX2R) but increased PVN AVP mRNA expression in SD rats. HS diet induced significant increases in MAP and PVN mRNA levels of Fra1, AVP, OX1R, and prepro orexin in DS rats. Intracerebroventricular (ICV) infusion of orexin A (0.2 nmol) increased PVN AVP mRNA levels in SD rats. Incubation of cultured hypothalamus neurons from newborn SD rats with orexin A resulted in increases in AVP mRNA expression which were attenuated by OX1R blockade. In addition increased cerebrospinal fluid (CSF) sodium concentration through ICV infusion of NaCl salt solution (4μmol) increased PVN OX1R and AVP mRNA levels in SD rats. Furthermore, bilateral PVN microinjection of the OX1R antagonist SB408124 resulted in a greater reduction in MAP in HS intake (-16±5 mmHg) compared to NS fed (-4±4 mmHg) anesthetized DS rats. These results suggest that elevated PVN OX1R activation may be involved in SSHTN through enhancing AVP signaling.

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