Abstract

Carbon monoxide (CO) is endogenously produced by heme oxygenase (HO) and CO may be an important signaling molecule in the vasculature including cerebral vessels. Endothelium-derived hyperpolarization factor (EDHF) relaxes blood vessels and may predominate over nitric oxide (NO) in resistance sized vessels. EDHF may also help to preserve vascular function in disease conditions where NO is reduced. This proposal will examine the role of CO in EDHF-mediated dilation in cerebral arteries. My preliminary data demonstrate that inhibition of HO with Cr(lll) mesoporphyrin IX (CrMP) blocks EDHF-mediated dilation to DTP in the rat middle cerebral artery (MCA). In the rat MCA, CO itself is not a dilator, however, in the presence of CrMP, exogenous CO restores EDHF-mediated dilation. These data suggest that CO plays a permissive-like role in EDHF-mediated dilation. This proposal will examine conditions in which CO is important for vasodilation in the rat MCA and will begin to examine the mechanism by which CO influences EDHF-mediated dilation in the rat MCA. Thus, this proposal brings together, for the first time, two important fields of study, CO and EDHF. ? ?

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32HL080916-02
Application #
7119598
Study Section
Special Emphasis Panel (ZRG1-F10 (20))
Program Officer
Meadows, Tawanna
Project Start
2005-09-06
Project End
2007-09-05
Budget Start
2006-09-06
Budget End
2007-09-05
Support Year
2
Fiscal Year
2006
Total Cost
$48,796
Indirect Cost

  Institution

Name
Baylor College of Medicine
Department
Anesthesiology
Type
Schools of Medicine
DUNS #
051113330
City
Houston
State
TX
Country
United States
Zip Code
77030

  Publications

Parelkar, Nikhil K; Silswal, Neerupma; Jansen, Kirsten et al. (2010) 2,2,2-trichloroethanol activates a nonclassical potassium channel in cerebrovascular smooth muscle and dilates the middle cerebral artery. J Pharmacol Exp Ther 332:803-10
Shafi, Nadeem I; Andresen, Jon; Marrelli, Sean P et al. (2008) Erythropoietin potentiates EDHF-mediated dilations in rat middle cerebral arteries. J Neurotrauma 25:257-65
Andresen, Jon J; Shafi, Nadeem I; Durante, William et al. (2006) Effects of carbon monoxide and heme oxygenase inhibitors in cerebral vessels of rats and mice. Am J Physiol Heart Circ Physiol 291:H223-30
Bryan Jr, Robert M; You, Junping; Phillips, Sharon C et al. (2006) Evidence for two-pore domain potassium channels in rat cerebral arteries. Am J Physiol Heart Circ Physiol 291:H770-80
Andresen, Jon; Shafi, Nadeem I; Bryan Jr, Robert M (2006) Endothelial influences on cerebrovascular tone. J Appl Physiol 100:318-27