Work

Crotonaldehyde paralyzes arteries by inducing impairment of ion channels, vascular histiocytic injury, overproduction of reactive oxygen species, mitochondrial damage, and autophagy

Year: 2024

Type: article

Abstract: Humans are ubiquitously exposed to crotonaldehyde (CRA) endogenously and exogenously. The effects and the mechanisms of CRA on arterial contractility need further elucidation. The present study demonstrated that instant exposure to CRA (1-300 μM) concentration-dependently declined the tension of pre-constricted arteries with a consequent irreversible depression on the arterial contractile responsiveness. Continuous exposure of rat coronary arteries (RCAs) to CRA concentration- and time-dependently depressed the arterial contractile responsiveness to various vasoconstrictors including depolarization, U46619, serotonin and agonist of voltage-gated Ca2+ channels (VGCCs). In enzymolysis-dispersed arterial smooth muscle cells (ASMCs) of RCAs, CRA abated depolarization-induced elevation of intracellular Ca2+ ([Ca2+]i). Electrophysiological study revealed that acute application of CRA depressed the functions of Ca2+-activated Cl- channels (CaCCs), voltage-gated K+ (Kv) channels and inward rectifier K+ (Kir) channels in RCA ASMCs. Prolonged culture of RCAs with CRA decreased expressions of VGCCs, CaCCs, Kv and Kir channels, disordered tissue frames of RCAs, injured arterial cells, and increased autophagosomes in both ASMCs and endothelial cells. Culture of rat aortic smooth muscle cells (A7r5) with CRA decreased the cell viability, elevated the intracellular levels of reactive oxygen species, reduced the mitochondrial membrane potential (MMP), and enhanced autophagy. Taken together, the present study evidenced that CRA decreased cell viability, depressed VGCCs, CaCCs, Kv channels and Kir channels, destroyed the arterial histiocytes, and finally paralyzed arteries, suggesting that the paralyzing effects of CRA on the arteries and their ASMCs are linked with excessive oxidative stress, mitochondrial dysfunction, and autophagy. The present results are helpful for the comprehensive evaluation of the vascular effects of CRA.

Source: Ecotoxicology and Environmental Safety

DOI: 10.1016/j.ecoenv.2024.117083