Lipid Peroxidation Product, Octanal, Impaired Corpora Cavernosa Reactivity in Mice

Erectile dysfunction is a common complication in males who have metabolic conditions. Diabetes, obesity, hypertension and other inflammatory conditions have a profound effect on the physiology of the penis because of elevated oxidative stress. Additionally, individuals who are overweight will typically have elevated unsaturated lipids and experience lipid peroxidation. As the name suggests, the lipids undergo oxidation from reactive oxygen species (ROS) and create a multitude of products. The objective of this study is to understand how aldehyde products of lipid peroxidation, such as octanal, affect the erectile tissue and peripheral vasculature in mice. Octanal is a medium chain aliphatic aldehyde that binds to olfactory receptor 2 (Olfr2). This aldehyde has been shown to induce the NLRP3 inflammasome, leading to the release of pro-inflammatory cytokines such as IL-1β and IL-18. We hypothesize that the lipid peroxidation product, octanal, will increase inflammasome activation and lead to sexual and vascular dysfunction. Corpora cavernosa (CC) were collected from 12-16 week old male C57BL/6 mice and mounted in a strip myograph to evaluate reactivity. The CCs underwent dose-response curves to phenylephrine (PE; 1 nM – 30 mM) and acetylcholine (Ach; 1 nM – 30 mM). Reactivity was repeated in the presence of octanal [10 μM (n=6-7) or 30 μM (n=3)] after a 30-minute incubation period. Nonlinear regression analysis was done to compare maximal responses (Emax) and the potency (pEC50) of the agonists. CCs were dissected and sections underwent a 24-hour incubation with 10uM octanal or octanal and citral (10 μM), an Olfr2 antagonist. Additionally, primary murine mesenteric resistance artery (MRA) endothelial cells (ECs) were cultured and incubated with octanal for 24 hours. Western blots were done to analyze caspase-1 and AIM2 inflammasome expression. The data were analyzed using GraphPad Prism, data sets were compared using Student’s T-Test with results displayed as mean +/- SEM. The CC displayed impaired relaxation (mN) to Ach in the presence of 30 μM octanal with decreased area under the curve (AUC) (control: 2.82 +/- 0.396 vs. octanal (30 μM) 1.34 +/- 0.14, p= 0.0278) and Emax [control: 0.9228 +/- 0.1651 vs. octanal (30 μM): 0.3939 +/- 0.035, p= 0.0455]. MRA ECs treated with 10 μM octanal for 24 hours exhibited a significant increase in caspase-1 expression [control: 0.9 +/- 0.1 vs. octanal (10 μM): 1.4, p= 0.0189] and a trending increase in AIM2 inflammasome expression. rtPCR analysis of the CC after octanal and citral treatment showed an increase in IL-1β expression that was reversed by the addition of citral in the incubation. These results are consistent with the notion that octanal, a lipid peroxidation product, induces the AIM2 inflammasome in the endothelium, leading to cavernosal dysfunction demonstrated by an impaired relaxation response to Ach. NIH DK132948: Institute on Cardiovascular Disease Research, Office for the Vice President for Research, University of South Carolina This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.