Abstract P1120: Opioids Induce Proliferation in Vascular Smooth Muscle Cells Leading to an Increase in Myogenic Tone in Resistance Arteries

Abstract

The United States of America is currently undergoing an opioid crisis. According to the 2018 CDC Annual Surveillance Report of Drug Related Risks and Outcomes there were 78,840 hospitalizations and an estimated 140,077 emergency room visits for opioid related poisonings in 2015 alone. It has been shown that opioid exposure increases vascular age relative to chronological age. Further, long-term abuse of opioids leads to changes in regional cerebral blood flow. However, there is a lack of understanding about acute and chronic opioid abuse and how it affects microvasculature structure and function; specifically on myogenic tone, a fundamental mechanism to maintain blood flow to important tissues including the brain, kidneys, and more. We hypothesize that opioids cause an increase in proliferation of vascular smooth muscle cells (VSMC) leading to an increase in myogenic tone in mesenteric resistance arteries. To test this hypothesis, aortic vascular smooth muscle cells were cultured and treated with the endogenous opioid (ENO) beta-endorphin or the exogenous opioid (EXO) morphine. ENO treatment increased cellular proliferation with chronic exposure (greater than 72 hours). We measured a maximum proliferation at 120 hours and performed 2 way ANOVA with Bonferroni posttests [confluence (%): DMSO vehicle 20.4 ± 4.8, 1 nM 34.9 ± 7.4*, and 1 μM 29.9 ± 7.0; * p<0.05]. Increased proliferation was also demonstrated in cells treated with EXO. We measured a maximum proliferation at 120 hours and performed 2 way ANOVA with Bonferroni posttests [confluence (%): DMSO vehicle 20.4 ± 4.8, 1 nM 32.6 ± 9.0, 1μM 33.3 ± 10.2*, and 10 μM 29.7 ± 4.4; * p<0.05]. We also observed that when acutely exposing mesenteric resistance arteries to EXO (1.0 μM) there was a left shift in myogenic tone to 80 mmHg as opposed to 100 mmHg in the in absence of EXO. In conclusion, our results suggest that chronic exposure to ENO and EXO increase VSMC proliferation. Further, acute exposure to EXO was able to increase myogenic tone in resistance arteries. This suggests that opioid dependence could contribute to the development of peripheral vascular disorders such as hypertension.