Vasoactivity of the gasotransmitters hydrogen sulfide and carbon monoxide in the chicken ductus arteriosus

Abstract

Besides nitric oxide (NO) and carbon monoxide (CO), hydrogen sulfide (H(2)S) is a third gaseous messenger that may play a role in controlling vascular tone and has been proposed to serve as an O(2) sensor. However, whether H(2)S is vasoactive in the ductus arteriosus (DA) has not yet been studied. We investigated, using wire myography, the mechanical responses induced by Na(2)S (1 μM-1 mM), which forms H(2)S and HS(-) in solution, and by authentic CO (0.1 μM-0.1 mM) in DA rings from 19-day chicken embryos. Na(2)S elicited a 100% relaxation (pD(2) 4.02) of 21% O(2)-contracted and a 50.3% relaxation of 62.5 mM KCl-contracted DA rings. Na(2)S-induced relaxation was not affected by presence of the NO synthase inhibitor l-NAME, the soluble guanylate cyclase (sGC) inhibitor ODQ, or the K(+) channel inhibitors tetraethylammonium (TEA; nonselective), 4-aminopyridine (4-AP, K(V)), glibenclamide (K(ATP)), iberiotoxin (BK(Ca)), TRAM-34 (IK(Ca)), and apamin (SK(Ca)). CO also relaxed O(2)-contracted (60.8% relaxation) and KCl-contracted (18.6% relaxation) DA rings. CO-induced relaxation was impaired by ODQ, TEA, and 4-AP (but not by L-NAME, glibenclamide, iberiotoxin, TRAM-34 or apamin), suggesting the involvement of sGC and K(V) channel stimulation. The presence of inhibitors of H(2)S or CO synthesis as well as the H(2)S precursor L-cysteine or the CO precursor hemin did not significantly affect the response of the DA to changes in O(2) tension. Endothelium-dependent and -independent relaxations were also unaffected. In conclusion, our results indicate that the gasotransmitters H(2)S and CO are vasoactive in the chicken DA but they do not suggest an important role for endogenous H(2)S or CO in the control of chicken ductal reactivity.

Molecular Mechanisms for Regulating Postnatal Ductus Arteriosus Closure

“…Interestingly, H 2 S was found to have biphasic effects, inducing vasoconstriction at lower concentrations while causing vasodilation at higher concentrations [ 30 ]. However, in the chicken DA, the vasodilatory effect was not shown [ 47 ]. The inter-species differences and dose-specific vasoreactive mechanisms of H 2 S in DA are not fully understood and warrant further investigations.…”

Evidence for a role of heme oxygenase-1 in the control of cardiac function in zebrafish (Danio rerio) larvae exposed to hypoxia

“…Furthermore, the amino acid sequence of the 'HO signature motif', believed to be important for heme binding and catabolism, shares 92-96% similarity between all vertebrate species investigated to date (Wang et al, 2008). Physiological control by endogenously produced CO is not restricted to mammalian vertebrates but is also involved in control of vascular tone and breathing in fish (Dombkowski et al, 2009;Tzaneva and Perry, 2014), retinal pathways and neuromuscular transmission in amphibians (Pong and Eldred, 2009;Sitdikova et al, 2007; reviewed in Sitdikova and Zefirov, 2012), and learning and vascular control in birds (Cutajar et al, 2005;Van der Sterren et al, 2011). Therefore, the HO-1/CO system appears to be a well conserved signalling pathway throughout all extant vertebrates.…”

Molecular and Mechanical Mechanisms Regulating Ductus Arteriosus Closure in Preterm Infants

“…Hem oxygenase 1 and hem oxygenase 2 which produce carbon monoxide (CO) are found in the endothelial and smooth muscle cells of the DA. CO dilates the ductus by inhibition of O 2 sensing cytochrome P450, thus interrupting endothelin-1 signaling ( 19 , 20 ) ( Figure 1 ). Carbon monoxide produced under physiological conditions seems to be negligible with regard to ductal patency but in cases of upregulation such as endotoxemia, it may have a relaxing effect on the ductus.…”