Recent advances in research on the force transmission mechanisms regulating endothelial function in the corpus cavernosum via fluid shear stress.

Penile erection is a precisely regulated vascular physiological process in which cavernous endothelial cells (CCECs) play a pivotal role in mechanical sensing and signal transduction. As a central biomechanical cue, fluid shear stress (FSS) is transduced by diverse mechanoreceptors on CCECs-including the glycocalyx, primary cilia, Piezo1 ion channels, and the PECAM-1 mechanosensory complex-resulting in the activation of endothelial nitric oxide synthase (eNOS) and nitric oxide (NO) production. This narrative review synthesizes the unique hemodynamic microenvironment of cavernous sinuses and the mechanical dynamics during the erectile cycle, focusing on the molecular mechanisms of mechanosensors and downstream signaling pathways regulating eNOS activity. Furthermore, the article elucidates how pathological conditions, such as atherosclerosis, hypertension, diabetes, aging, and microvascular sclerosis, induce endothelial dysfunction and vascular erectile dysfunction (ED) through perturbed mechanical microenvironments or damage to sensory structures. Finally, this paper proposes that targeting mechanotransduction pathways may offer novel strategies for preventing and treating ED and delineates promising directions for future investigations.