In Utero Morphine Exposure Induces Hypertension And Opioid Receptor‐Mediated Angiotensin II Sensitization

Opioid use disorder (OUD) is associated with nearly two‐fold increased risk of cardiovascular disease, metabolic syndrome and diabetes. OUD by pregnant women is an understudied area related to the opioid epidemic leading to increased incidence of neonatal abstinence syndrome (NAS) and neonatal opioid withdrawal syndrome (NOWS). There is an interaction between the Renin‐Angiotensin System (RAS) and the endogenous opioid system (EOS) commonly associated with the development of hypertension. This study tests the hypothesis that in utero opioid exposure induces hypertension and increases vascular reactivity to Angiotensin‐II (AngII) in the adult offspring. Sprague Dawley dams were treated with escalating doses of a mu‐opioid receptor agonist morphine (MOR, 5‐20mg/kg/day, s.c) or saline (VEH). Weight gain was not different between MOR and VEH‐exposed pregnant rats (F‐MOR 100.2±9.5 vs F‐VEH 95±10 g, n=4, p=NS). Additionally, litter size was not different (F‐MOR13.75±0.2 vs F‐VEH 12.25±1.8 pups, n=4, p=NS). However, MOR‐exposed females exhibited low birth weight (F‐MOR 5.6±0.2 vs F‐VEH 7.2±0.6 g, n=20‐22, p