Single Prolonged Stress Alters Vasopressin and Orexin System Expression in Sprague Dawley Rats

Posttraumatic stress disorder (PTSD) is a complex psychiatric disorder triggered by a terrifying event, causing severe anxiety and nightmares. Studies showed that patients with PTSD have increased risk of cardiovascular disease. However, the effect of PTSD on blood pressure remains unraveled. In this study, we test the hypothesis that PTSD alters expression of arginine vasopressin (AVP) and orexin system components and therefore increases blood pressure. Single prolonged stress (SPS) protocol including 2 hours of restraint, a 20-min forced swimming and exposure to diethyl ether until loss of consciousness was used to create a PTSD model. Eight-week-old male Sprague Dawley (SD) rats were divided into two groups and treated with or without SPS, then all rats were single-housed and remained undisturbed for 7 days. Their blood pressure (BP) and heart rates (HR) were recorded by radio telemetry transmitter system (Data Science International) prior to the treatment as baseline, and 1- day, and 7-day post the treatment. The data showed that SPS significantly increased BP (Δ BP: 8.384 ± 1.187 mmHg, N = 6 P \u3c 0.05) and HR (Δ HR: 32.88 ± 9.149 beats/min, N = 6 P \u3c 0.05) compared to control rats (Δ BP: 2.346 ± 0.9324 mmHg, Δ HR: -1.503 ± 5.960 beats/min, N = 8) on day 1 post treatment, but no significance difference was observed in BP and HR on day 7 compared to their own baseline and between SPS and control groups. To investigate whether AVP and orexin systems participate in PTSD development, we examined paraventricular nucleus (PVN) and adrenal gland AVP- and orexin receptor 1 (OX1R) and orexin receptor 2 (OX2R) expression in both SD male and female rats with or without SPS at day 7. Our data showed that PVN AVP mRNA levels were increased by 2-fold in the SPS group compared to control in male rats (P \u3c 0.05) but this change was not observed in female rats. No changes were observed in PVN OX1R and OX2R mRNA levels between SPS and control rats in both males and females. Peripheral orexin receptors\u27 protein levels were altered but showed inconsistency in male and female rats: western blot data showed that adrenal gland OX1R protein levels were increased in the SPS group (control: 1.000 ± 0.07424 N=5 vs SPS: 1.531 ± 0.2016 N = 5; P \u3c 0.05) in male rats, while OX2R protein levels were decreased in female rats in female rats (control: 1.000 ± 0.01025 N = 5 vs SPS: 0.8840 ± 0.04533 N = 6; P \u3c 0.05). Renal OX1R was also increased (control: 1.000 ± 0.02794 N = 3 vs SPS: 1.374 ± 0.1385 N = 3; P \u3c 0.06) in female rats under SPS. ELISA assay showed that plasma orexin A levels were increased in female rats under SPS (control: 1.000 ± 0.1600 pg/mL N = 3 vs SPS: 1.561 ± 0.1262 pg/mL; N = 3 P \u3c 0.05) but not in male rats. These results suggested that the central AVP system and peripheral orexin system may play a role in PTSD-related high blood pressure development, and the peripheral orexin system may mediate stress response of female rats more than male rats. These molecular differences between SD male and female rats may also help to answer why females and males showed different responses to trauma. Further study will continue to find the PTSD-sensitized hypertensive model and investigate specific functions of AVP and orexin system in PTSD