title: Gene transfer of cystathionine β-synthase into RVLM increases hydrogen sulfide-mediated suppression of sympathetic outflow via KATP channel in normotensive rats.
abstract: Hydrogen sulfide has been shown to have a sympathoinhibitory effect in the rostral ventrolateral medulla (RVLM). The present study examined the function of cystathionine β-synthase (CBS)/hydrogen sulfide system in the RVLM, which plays a crucial role in the control of blood pressure and sympathetic nerve activity. Adenovirus vectors encoding CBS (AdCBS) or enhanced green fluorescent protein (AdEGFP) were transfected into the RVLM in normotensive rats. Identical microinjection of AdCBS into the RVLM had no effect on systolic blood pressure and heart rate (HR) in conscious rats. Acute experiments were performed at day 7 after gene transfer in anesthetized rats. Microinjection of the CBS inhibitors hydroxylamine (HA) or amino-oxyacetate into the RVLM produced an increase in the renal sympathetic nerve activity (RSNA), mean arterial pressure (MAP), and HR. There was a potentiation of the increases in RSNA, MAP, and HR because of the CBS inhibitors in AdCBS-injected rats compared with AdEGFP-injected rats. Pretreatment with pinacidil, a ATP-sensitive potassium (KATP) channel activator, abolished the effects of HA in two groups. Microinjection of glibenclamide, a KATP channel blocker, produced increases in RSNA, MAP, and HR in AdCBS-injected rats. No changes in behavior were observed in AdEGFP-injected rats. Furthermore, Western blot analysis indicated an increase in the expression of sulfonylurea receptor 2 and inward rectifier K(+) 6.1 in AdCBS-injected rats. These results suggest that the increase in KATP channels in the RVLM may be responsible for the greater sympathetic outflow and pressor effect of HA in AdCBS-injected rats compared with AdEGFP-injected rats.
authors.affiliation: Department of Physiology, Institute of Basic Medicine, Hebei Medical University, Shijiazhuang, China; Hebei Key Lab of Laboratory Animal Science, Department of Laboratory Animal Science, Hebei Medical University, Shijiazhuang, China; and.
authors.forename: Xiao-cui
authors.initials: XC
authors.lastname: Duan
authors.affiliation: Dean's Office of the Third Hospital of Hebei Medical University, Shijiazhuang, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Guo
authors.affiliation: Department of Physiology, Institute of Basic Medicine, Hebei Medical University, Shijiazhuang, China;
authors.forename: Shang-yu
authors.initials: SY
authors.lastname: Liu
authors.affiliation: Department of Physiology, Institute of Basic Medicine, Hebei Medical University, Shijiazhuang, China;
authors.forename: Lin
authors.initials: L
authors.lastname: Xiao
authors.affiliation: Department of Physiology, Institute of Basic Medicine, Hebei Medical University, Shijiazhuang, China;
authors.forename: Hong-mei
authors.initials: HM
authors.lastname: Xue
authors.affiliation: Department of Physiology, Institute of Basic Medicine, Hebei Medical University, Shijiazhuang, China;
authors.forename: Qi
authors.initials: Q
authors.lastname: Guo
authors.affiliation: Department of Physiology, Institute of Basic Medicine, Hebei Medical University, Shijiazhuang, China;
authors.forename: Sheng
authors.initials: S
authors.lastname: Jin
authors.affiliation: Department of Physiology, Institute of Basic Medicine, Hebei Medical University, Shijiazhuang, China; wuyum@yahoo.com.
authors.forename: Yu-ming
authors.initials: YM
authors.lastname: Wu
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D062186:Arterial Pressure; D002319:Cardiovascular System / Q000294:innervation*; D003541:Cystathionine beta-Synthase / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D006339:Heart Rate; D006862:Hydrogen Sulfide / Q000378:metabolism*; D054086:KATP Channels / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007668:Kidney / Q000294:innervation*; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects / Q000201:enzymology*; D009433:Neural Inhibition / Q000187:drug effects; D026902:Potassium Channel Blockers / Q000494:pharmacology; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D064233:Sulfonylurea Receptors / Q000378:metabolism; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D013997:Time Factors; D015854:Up-Regulation
chemical_list: C577512:Abcc9 protein, rat; D004791:Enzyme Inhibitors; D054086:KATP Channels; D026902:Potassium Channel Blockers; D064233:Sulfonylurea Receptors; C092520:uK-ATP-1 potassium channel; D003541:Cystathionine beta-Synthase; D006862:Hydrogen Sulfide
keywords: blood pressure; cystathionine β-synthase; gene transfer; renal sympathetic nerve activity; rostral ventrolateral medulla