Hydrogen sulfide downregulates the aortic l-arginine/nitric oxide pathway in rats

Abstract

The aim of the present study was to investigate the effect of hydrogen sulfide (H(2)S) signaling by nitric oxide (NO) in isolated rat aortas and cultured human umbilical vein endothelial cells (HUVECs). Both administration of H(2)S and NaHS, as well as endogenous H(2)S, reduced NO formation, endothelial nitric oxide synthase (eNOS) activity, eNOS transcript abundance, and l-arginine (l-Arg) transport (all P < 0.01). The kinetics analysis of eNOS activity and l-Arg transport showed that H(2)S reduced V(max) values (all P < 0.01) without modifying K(m) parameters. Use of selective NOS inhibitors verified that eNOS [vs. inducible NOS (iNOS) and neuronal NOS (nNOS)] was the specific target of H(2)S regulation. H(2)S treatment (100 micromol/l) reduced Akt phosphorylation and decreased eNOS phosphorylation at Ser1177. H(2)S reduced l-Arg uptake by inhibition of a system y+ transporter and decreased the CAT-1 transcript. H(2)S treatment reduced protein expression of eNOS but not of nNOS and iNOS. Pinacidil (K(ATP) channel opener) exhibited the similar inhibitory effects on the l-Arg/NOS/NO pathway. Glibenclamide (K(ATP) channel inhibitor) partly blocked the inhibitory effect of H(2)S and pinacidil. An in vivo experiment revealed that H(2)S downregulated the vascular l-Arg/eNOS/NO pathway after intraperitoneal injection of NaHS (14 micromol/kg) in rats. Taken together, our findings suggest that H(2)S downregulates the vascular l-Arg/NOS/NO pathway in vitro and in vivo, and the K(ATP) channel could be involved in the regulatory mechanism of H(2)S.

Characterization of a Novel, Water-Soluble Hydrogen Sulfide–Releasing Molecule (GYY4137)

“…25 However, higher doses caused a biphasic relaxation/constriction response, the mechanism of which warrants further study. H 2 S can contract isolated blood vessels either by quenching released NO, 13 by inhibiting endothelial NO synthase, 26 or by oxidation of H 2 S to a vasoconstrictor molecule in conditions of high oxygen tension. 27 Bolus injection of GYY4137 did not affect renal perfusion pressure, presumably because the drug is washed out of the tissue before sufficient breakdown to H 2 S occurs.…”

Hydrogen sulfide triggers late-phase preconditioning in postischemic small intestine by an NO- and p38 MAPK-dependent mechanism

“…In addition, the production of H 2 S can be upregulated by NO (49,57). Most recently, Geng et al (17) have shown that eNOS (vs. inducible NOS and neuronal NOS) may be the specific target of H 2 S regulation in rat aortas (50). Thus we evaluated the role of eNOS in the vasculoprotection afforded by late-phase H 2 S-PC by employing a pharmacological inhibitor approach in WT animals and using an eNOS knockout model.…”

Regulation of Colonic Ion Transport by Gasotransmitters

“…24) Two main intracellular action sites of H 2 S are known from different cell systems. This includes the ability of H 2 S to stimulate ATPsensitive K ϩ channels, an effect that is well characterized e.g.…”