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Piezo1 channel is a sensor for shear-stress in the vasculature. Piezo1 activation induces vasodilation, and its deficiency contributes to vascular disorders, such as hypertension. In this study, we aimed to determine whether Piezo1 channel has a functional role in the dilation of pudendal arteries and corpus cavernosum (CC). For this, male Wistar rats were used, and the relaxation of the pudendal artery and CC was obtained using the Piezo1 activator, Yoda1, in the presence and absence of Dooku (Yoda1 antagonist), GsMTx4 (non-selective mechanosensory channel inhibitor) and L-NAME (nitric oxide synthase inhibitor). In the CC, Yoda1 was also tested in the presence of indomethacin (non-selective COX inhibitor) and tetraethylammonium (TEA, non-selective potassium channel inhibitor). The expression of Piezo1 was confirmed by Western blotting. Our data show that Piezo1 activation leads to the relaxation of the pudendal artery and CC as the chemical activator of Piezo1, Yoda1, relaxed the pudendal artery (47%) and CC (41%). This response was impaired by L-NAME and abolished by Dooku and GsMTx4 in the pudendal artery only. Indomethacin and TEA did not affect the relaxation induced by Yoda1 in the CC. Limited tools to explore this channel prevent further investigation of its underlying mechanisms of action. In conclusion, our data demonstrate that Piezo1 is expressed and induced the relaxation of the pudendal artery and CC. Further studies are necessary to determine its role in penile erection and if erectile dysfunction is associated with Piezo1 deficiency. more...

Hypoxic environments at high altitude have significant effects on kidney injury. Following injury, renal primary cilia display length alterations. Primary cilia are mechanosensory organelles that regulate tubular architecture. The effect of hypoxia on cilia length is still controversial in cultured cells, and no corresponding in vivo study exists. Using fetal and adult sheep, we here study the effect of chronic hypobaric hypoxia on the renal injury, intracellular calcium signaling and the relationship between cilia length and cilia function. Our results show that although long-term hypoxia induces renal fibrosis in both fetal and adult kidneys, fetal kidneys are more susceptible to hypoxia-induced renal injury. Unlike hypoxic adult kidneys, hypoxic fetal kidneys are characterized by interstitial edema, tubular disparition and atrophy. We also noted that there is an increase in the cilia length as well as an increase in the cilia function in the hypoxic fetal proximal and distal collecting epithelia. Hypoxia, however, has no significant effect on primary cilia in the adult kidneys. Increased cilia length is also associated with greater flow-induced intracellular calcium signaling in renal epithelial cells from hypoxic fetuses. Our studies suggest that while hypoxia causes renal fibrosis in both adult and fetal kidneys, hypoxia-induced alteration in cilia length and function are specific to more severe renal injuries in fetal hypoxic kidneys. more...

Hypoxic environments at high altitude have significant effects on kidney injury. Following injury, renal primary cilia display length alterations. Primary cilia are mechanosensory organelles that regulate tubular architecture. The effect of hypoxia on cilia length is still controversial in cultured cells, and no corresponding in vivo study exists. Using fetal and adult sheep, we here study the effect of chronic hypobaric hypoxia on the renal injury, intracellular calcium signaling and the relationship between cilia length and cilia function. Our results show that although long-term hypoxia induces renal fibrosis in both fetal and adult kidneys, fetal kidneys are more susceptible to hypoxia-induced renal injury. Unlike hypoxic adult kidneys, hypoxic fetal kidneys are characterized by interstitial edema, tubular disparition and atrophy. We also noted that there is an increase in the cilia length as well as an increase in the cilia function in the hypoxic fetal proximal and distal collecting epithelia. Hypoxia, however, has no significant effect on primary cilia in the adult kidneys. Increased cilia length is also associated with greater flow-induced intracellular calcium signaling in renal epithelial cells from hypoxic fetuses. Our studies suggest that while hypoxia causes renal fibrosis in both adult and fetal kidneys, hypoxia-induced alteration in cilia length and function are specific to more severe renal injuries in fetal hypoxic kidneys. [ABSTRACT FROM AUTHOR] more...