In utero Morphine Exposure Increases Blood Pressure in Association with Increased Markers of Sympathetic Activation in the Adult Offspring

The opioid overdose and opioid use disorder (OUD) epidemics are concomitant with nearly a 2-fold increased risk of cardiovascular disease (CVD). Opioid abuse during pregnancy increases the incidence of neonatal opioid withdrawal syndrome (NOWS) by 5-fold; however, the long-term effects on the offspring’s cardiovascular health are understudied. Previously, we have shown that both male and female offspring from dams exposed to mu-opioid receptor agonist morphine (MOR) during pregnancy display high blood pressure and reduced renal function as adults. Further, cardiovascular tissues of MOR-exposed offspring show downregulation of the endogenous opioid peptide proenkephalin (PENK) mRNA expression, which has been shown to play a role in modulating the adrenergic receptors signaling. This study aimed to investigate whether increased blood pressure in MOR-exposed offspring is associated with the activation of the sympathetic system.Sprague Dawley dams were treated with escalating doses of MOR (5-20 mg/kg/day, s.c) or saline (VEH) from gestational day 1 to 18. At 16 weeks, rats were implanted with femoral artery catheters for direct blood pressure measurements in response to the alpha-adrenergic receptor (A-ADR) blocker doxazosin (4 mg/kg/day, s.c) or saline. At the end of the study, plasma norepinephrine (NE) was measured by HPLC, and brain micropunches of the paraventricular nucleus of the hypothalamus (PVN), implicated in blood pressure regulation, were collected for RNAseq analysis.MOR-exposed offspring showed a greater reduction in the pressor response to mecamylamine (5 mg/kg, IP, delta change in mmHg: F-MOR -44.9±5.8 vs F-VEH -18.3±1.3, p0.05, n=6-8). Renal mRNA expression of the alpha-adrenergic receptor was downregulated ~3-fold (-2ddCt n=6-8, p HL135158 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.