Abstract P100: Opioids Cause Sex-Specific Vascular Remodeling Via Cofilin-ERK Signaling: Female Mice Present Higher Risk Of Developing Morphine-Induced Vascular Dysfunction Than Male Mice Meeting Abstract (Web of Science)

abstract

  • Recent studies have shown that chronic use of prescription opioids leads to increased risk of cardiovascular events and pulmonary arterial hypertension. Indices of vascular age and arterial stiffness are increased in opioid dependent patients and the effects are more marked in women. We hypothesized that chronic exposure to exogenous opioids causes sex-specific vascular remodeling via suppression of actin depolymerization. Using culture pressure myographs, we performed continuous intraluminal infusion of morphine (10μM for 24 hours) in pressurized mesenteric resistance arteries (MRA, fifth order) from male and female mice (C57BL/6NTac, 10 weeks old; n=4). Intraluminal pressure curve showed that morphine reduced lumen diameter by 23% (without morphine: 185 ± 10μm vs. morphine: 143 ± 14μm*) in MRA from female mice, whereas little to no change was observed in MRA from male mice (Fig. 1). Cofilin is a key molecule in preventing stress fiber overassembly and is inactivated by extracellular signal-regulated kinases (ERK). Here, we observed that after 24-hour exposure, morphine (10μM) phosphorylated and inactivated cofilin 1.6 fold [AU: control: 0.59 ± 0.14 vs. morphine: 0.95 ± 0.10*, *p<0.05, t-test] and increased ERK phosphorylation 1.8 fold (AU: control: 0.51 ± 0.11 vs. morphine: 0.90 ± 0.13*, *p<0.05) in MRA from female mice. On the other hand, morphine decreased phospho-ERK 1.5 fold (AU: control: 0.91 ± 0.08 vs. morphine: 0.59 ± 0.11*, *p<0.05) but had no effect on the levels of cofilin in MRA from male mice. These results have significant implications for the previously unexplored role of exogenous opioids as a modifiable cardiovascular risk factor, particularly in women.

authors

  • Cheon, Soyoung
  • Edwards, Jonnelle M
  • Tomcho, Jeremy C
  • Bearss, Nicole R
  • Joe, Bina
  • McCarthy, Cameron G
  • Wenceslau, Camilla F

publication date

  • 2020

published in

volume

  • 76

issue

  • Suppl_1