Mechanisms Associated to Nitroxyl (HNO)-Induced Relaxation in the Intestinal Smooth Muscle

Contractility of isolated colonic smooth muscle strips from rats treated with cancer chemotherapy: differential effects of cisplatin and vincristine

“…When initial and final KCl responses were compared throughout the experiment, a slight decrease in the phasic and tonic responses of both muscle preparations was observed, except for PA in LM of cohort 2, which showed a slight increase in both control and vincristine groups. However, these modifications were not statistically significant, indicating that the responses were minimally affected by the study protocol ( Gastreich-Seelig et al, 2020 ). The only notable difference between the two cohorts at baseline occurred in the phasic component of the CM, with cohort 1 displaying a greater response than cohort 2 ( Figure 4B ).…”

“…The PA produced by ACh is caused by the release of calcium from intracellular organelles ( Zhou et al, 2008 ). Specifically, ACh binds to G-protein-coupled muscarinic receptors, which initiate a physiological cascade through G αq/11 leading to activation of phospholipase Cβ and synthesis of inositol 1,4,5-trisphosphate (IP 3 ), which binds to its receptor (IP 3 R) in the sarcoplasmic reticulum and results in intracellular Ca 2+ release ( Gastreich-Seelig et al, 2020 ). In contrast, TA is evoked by an increase in extracellular Ca 2+ influx through voltage-dependent Ca 2+ channels ( Zhou et al, 2008 ).…”

“…were not statistically significant, indicating that the responses were minimally affected by the study protocol (Gastreich-Seelig et al, 2020). The only notable difference between the two cohorts at baseline occurred in the phasic component of the CM, with cohort 1 displaying a greater response than cohort 2 (Figure 4B).…”

Nitroxyl Delivered by Angeli’s Salt Causes Short-Lasting Activation Followed by Long-Lasting Deactivation of Meningeal Afferents in Models of Headache Generation

“…Having shown that the vigorous activation of primary meningeal afferents by Angeli's salt is obviously not or not alone dependent on TRPA1 receptor channels, we find that the question arises as to which other mechanisms come into account for this phenomenon. In the submucosa of the colon and the ileum, HNO formed by Angeli's salt has been shown to activate basolateral K + channels and the Na + -K + -ATPase [19], most likely via the sGC-cGMP (soluble guanylate cyclase-cyclic guanosine monophosphate) pathway [20], which results in smooth muscular relaxation [21]. Similar mechanisms have been described involving voltage-dependent K + channels and ATP-sensitive K + channels (K ATP ) of smooth arterial muscle [22,23].…”

Using In Silico Tools To Map the Structural Landscape of Nitroxyl (HNO Donor) Compounds

“…HNO donor compounds (specifically N -hydroxysulfonamide derivatives) have emerged as a new class of potential pharmaceutics pertinent to the management of heart failure. − These compounds play an important role in protecting the cardiovascular system from further damage during heart failure and in restoring function to organs affected by this debilitating condition. ,, Various HNO donor compounds have been developed through structural modifications to understand their chemical and physical properties while keeping the HNO N -hydroxysulfonamide moiety in common. , Recent investigations of HNO donor compounds as APIs have underscored the necessity of understanding the solid form landscape of these materials; however, a search of the Cambridge Structural Database (CSD, v5.41) shows that there is a lack of structures available containing the N -hydroxysulfonamide moiety. By using these compounds as test cases, we can therefore highlight the utility of employing simple algorithms to predict structure-directing intermolecular interactions in crystalline forms of APIs.…”