Novel soluble guanylyl cyclase stimulator BAY 41-2272 attenuates ischemia-reperfusion-induced lung injury

Abstract

Egemnazarov B, Sydykov A, Schermuly RT, Weissmann N, Stasch JP, Sarybaev AS, Seeger W, Grimminger F, Ghofrani HA. Novel soluble guanylyl cyclase stimulator BAY 41-2272 attenuates ischemia-reperfusion-induced lung injury.

Stimulators of soluble guanylate cyclase (sGC) inhibit experimental skin fibrosis of different aetiologies

“…These findings suggest a role for riociguat for the treatment of SSc. Moreover, sGC stimulation has also been shown to ameliorate fibrosis in other organs commonly affected in SSc such as the lungs and the heart 18 19. These findings suggest a role for riociguat for the treatment of fibrotic diseases, especially for the treatment of SSc-driven internal organ involvement.…”

cGMP-Dependent Protein Kinases and cGMP Phosphodiesterases in Nitric Oxide and cGMP Action

“…Activation of NO-GC by some of these (e.g., BAY 41-2272) is dependent on the heme moiety and synergizes with effects of NO. Activation by other compounds occurs via a NO-independent, hemedependent action or a NO-and heme-independent process (e.g., BAY 58-2667) (Straub et al, 2001;Stasch et al, 2002;Schmidt et al, 2003;Egemnazarov et al, 2009;Stasch and Hobbs, 2009).…”

“…Appreciation of the importance and complexity of the actions of NO/cGMP/PKGI signaling in diverse vascular tissues is driving the search for improved new therapies for systemic hypertension, cardiac failure, 528 cardiac reperfusion injury, vascular smooth muscle proliferation, atherogenesis, endothelial dysfunction, and Raynaud's disease. Renewed efforts are also afoot to identify drugs and treatment strategies that influence this signaling pathway because of the potential for pharmacological relief of malfunctions in nonvascular cell types as well Bryan et al, 2009;Egemnazarov et al, 2009;Hofmann et al, 2009;Kleppisch and Feil, 2009;Krieg et al, 2009;Lapp et al, 2009;Reaume and Sokolowski, 2009). Effective medications that foster NO/cGMP/PKGI signaling in penile and pulmonary vascular beds have already provided the lead to major advances and hold promise for treatment of other maladies.…”

The Janus-faced regulation of endothelial permeability by cyclic GMP

“…The barrier-enhancing properties of cGMP were further substantiated by use of a group of recently identified sGC stimulators and activators that either amplify NO-induced cGMP formation by native (reduced) sGC, or induce cGMP generation from heme-free or oxidized sGC independent of NO, respectively (18). In line with the proposed barrier protection by cGMP, the sGC stimulator BAY 41-2272 was shown to reduce lung vascular permeability in models of overventilation (17), elevated lung vascular pressures (24), or pulmonary ischemia-reperfusion injury (2).…”