| First Author | Sobrano Fais R | Year | 2023 |
| Journal | J Cell Mol Med | Volume | 27 |
| Issue | 1 | Pages | 1-14 |
| PubMed ID | 36515571 | Mgi Jnum | J:351474 |
| Mgi Id | MGI:7424225 | Doi | 10.1111/jcmm.17463 |
| Citation | Sobrano Fais R, et al. (2023) NLRP3 activation contributes to endothelin-1-induced erectile dysfunction. J Cell Mol Med 27(1):1-14 |
| abstractText | In the present study, we hypothesized that endothelin (ET) receptors (ET(A) and ET(B) ) stimulation, through increased calcium and ROS formation, leads to Nucleotide Oligomerization Domain-Like Receptor Family, Pyrin Domain Containing 3 (NLRP3) activation. Intracavernosal pressure (ICP/MAP) was measured in C57BL/6 (WT) mice. Functional and immunoblotting assays were performed in corpora cavernosa (CC) strips from WT, NLRP3(-/-) and caspase(-/-) mice in the presence of ET-1 (100 nM) and vehicle, MCC950, tiron, BAPTA AM, BQ123, or BQ788. ET-1 reduced the ICP/MAP in WT mice, and MCC950 prevented the ET-1 effect. ET-1 decreased CC ACh-, sodium nitroprusside (SNP)-induced relaxation, and increased caspase-1 expression. BQ123 an ET(A) receptor antagonist reversed the effect. The ET(B) receptor antagonist BQ788 also reversed ET-1 inhibition of ACh and SNP relaxation. Additionally, tiron, BAPTA AM, and NLRP3 genetic deletion prevented the ET-1-induced loss of ACh and SNP relaxation. Moreover, BQ123 diminished CC caspase-1 expression, while BQ788 increased caspase-1 and IL-1beta levels in a concentration-dependent manner (100 nM-10 muM). Furthermore, tiron and BAPTA AM prevented ET-1-induced increase in caspase-1. In addition, BAPTA AM blocked ET-1-induced ROS generation. In conclusion, ET-1-induced erectile dysfunction depends on ET(A) - and ET(B) -mediated activation of NLRP3 in mouse CC via Ca(2+) -dependent ROS generation. |
