Estrogen Increases Smooth Muscle Expression of alpha2C-Adrenoceptors and Cold-Induced Constriction of Cutaneous Arteries

Details

• Personal Author:
  Bailey SR ; Chotani MA ; Eid AH ; Flavahan NA ; Flavahan S ; Maiti K ; Mitra S ; Thompson-Torgerson CS
• Description:
  Raynaud's phenomenon, which is characterized by intense cold-induced constriction of cutaneous arteries, is more common in women compared with men. Cold-induced constriction is mediated in part by enhanced activity of alpha(2C)-adrenoceptors (alpha(2C)-ARs) located on vascular smooth muscle cells (VSMs). Experiments were therefore performed to determine whether 17beta-estradiol regulates alpha(2C)-AR expression and function in cutaneous VSMs. 17beta-Estradiol (0.01-10 nmol/l) increased expression of the alpha(2C)-AR protein and the activity of the alpha(2C)-AR gene promoter in human cultured dermal VSMs, which was assessed following transient transfection of the cells with a promoter-reporter construct. The effect of 17beta-estradiol was associated with increased accumulation of cAMP and activation of the cAMP-responsive Rap2 GTP-binding protein. Transient transfection of VSMs with a dominant-negative mutant of Rap2 inhibited the 17beta-estradiol-induced activation of the alpha(2C)-AR gene promoter, whereas a constitutively active mutant of Rap2 increased alpha(2C)-AR promoter activity. The effects of 17beta-estradiol were inhibited by the estrogen receptor (ER) antagonist, ICI-182780 (1 micromol/l), and were mimicked by a cell-impermeable form of the hormone (estrogen:BSA) or by the selective ER-alpha receptor agonist 4,4',4'''-(4-propyl-[(1)H]-pyrazole-1,3,5-triyl)tris-phenol (PPT; 10 nmol/l) or the selective ER-beta receptor agonist 2,3-bis(4-hydroxyphenyl)-propionitrile (DPN; 10 nmol/l). Therefore, 17beta-estradiol increased expression of alpha(2C)-ARs by interacting with cell surface receptors to cause a cAMP/Rap2-dependent increase in alpha(2C)-AR transcription. In mouse tail arteries, 17beta-estradiol (10 nmol/l) increased alpha(2C)-AR expression and selectively increased the cold-induced amplification of alpha(2)-AR constriction, which is mediated by alpha(2C)-ARs. An estrogen-dependent increase in expression of cold-sensitive alpha(2C)-ARs may contribute to the increased activity of cold-induced vasoconstriction under estrogen-replete conditions. [Description provided by NIOSH]
• Subjects:
  Coal Coal Mining Dust Environmental Monitoring Laboratories Mining Occupational Health Safety
• Keywords:
  Animal-studies Blood-vessels Enzymes Genes Hormone-activity Hormones Muscle-cells Proteins Vasoactive-agents
• ISSN:
  0363-6135
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  Maryland ; Ohio ; OSHA Region 3 ; OSHA Region 5
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  293
• Issue:
  3
• NIOSHTIC Number:
  nn:20032779
• Citation:
  Am J Physiol Heart Circ Physiol 2007 Sep; 293(3):H1955-H1961
• Contact Point Address:
  N. A. Flavahan, Dept. of Anesthesiology and Critical Care Medicine, Johns Hopkins University, Ross Research Bldg., R 370/372, 720 Rutland Ave., Baltimore, MD 21205
• Email:
  nflavah1@jhmi.edu
• Federal Fiscal Year:
  2007
• Performing Organization:
  Jonhs Hopkins University
• Peer Reviewed:
  True
• Start Date:
  20050801
• Source Full Name:
  American Journal of Physiology - Heart and Circulatory Physiology
• End Date:
  20100731
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:e55a1831944010e11dec75533851392fcb7a9667fed3523d136c5a2a07647e374398a8e3df1f0a048eb9b7f0f1edf6de48337dec30133c80f1781717749817e5
• Download URL:
  https://stacks.cdc.gov/view/cdc/186624/cdc_186624_DS1.pdf
• File Type:
  [PDF - 159.48 KB ]