Acetylcholine- and sodium hydrosulfide-induced endothelium-dependent relaxation and hyperpolarization in cerebral vessels of global cerebral ischemia-reperfusion rat.

Abstract

We investigated the effects of endothelium-derived hyperpolarizing factor (EDHF) and the role of hydrogen sulphide (H2S) in the cerebral vasorelaxation induced by acetylcholine (ACh) in global cerebral ischemia-reperfusion (CIR) rats. CIR was induced by occlusion of bilateral carotid and vertebral arteries. Isolated arterial segments from the cerebral basilar (CBA) and middle artery (MCA) of CIR rats were studied in a pressurized chamber. Transmembrane potential was recorded using glass microelectrodes to evaluate hyperpolarization. In the CIR CBAs and MCAs preconstricted by 30 mM KCl, ACh induced concentration-dependent vasorelaxation and hyperpolarization that were partially attenuated by NG-nitro-l-arginine methyl ester (l-NAME, 30 μM) and l-NAME plus indomethacin (10 μM). The residual responses were abolished by the H2S inhibitor dl-propargylglycine (PPG, 100 μM). The H2S donor NaHS and l-Cys, the substrate of endogenous H2S synthase, elicited similar responses to ACh and was inhibited by tetraethylamonine (1 mM) or PPG. ACh induces EDHF-mediated vasorelaxation and hyperpolarization in rat cerebral arteries. These responses are up-regulated by ischemia-reperfusion while NO-mediated responses are down-regulated. Further, the ACh-induced, EDHF-mediated relaxation, and hyperpolarization and the inhibition of these responses are similar to the H2S-induced responses, suggesting that H2S is a possible candidate for EDHF in rat cerebral vessels.

• Authors: Jun Han, Zhi-Wu Chen, Guo-Wei He
• Journal: Journal of pharmacological sciences (J Pharmacol Sci) Vol. 121 Issue 4 Pg. 318-26 ( 2013) ISSN: 1347-8648 [Electronic] Japan
• PMID: 23603896 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biological Factors
• Sulfides
• endothelium-dependent hyperpolarization factor
• sodium bisulfide
• Acetylcholine
• Hydrogen Sulfide

Topics

• Acetylcholine (pharmacology)
• Animals
• Biological Factors (physiology)
• Cerebral Arteries (drug effects)
• Disease Models, Animal
• Endothelium, Vascular (physiology)
• Hydrogen Sulfide
• In Vitro Techniques
• Male
• Muscle Relaxation (drug effects)
• Muscle, Smooth, Vascular (drug effects)
• Rats
• Rats, Sprague-Dawley
• Reperfusion Injury (physiopathology)
• Sulfides (pharmacology)