Acute Dilation to alpha(2)-Adrenoceptor Antagonists Uncovers Dual Constriction and Dilation Mediated by Arterial alpha(2)-Adrenoceptors

Details

• Personal Author:
  Crassous PA ; Flavahan NA ; Flavahan S
• Description:
  BACKGROUND AND PURPOSE: In mouse tail arteries, selective alpha(2)-adrenoceptor antagonism with rauwolscine caused powerful dilation during constriction to the alpha(1)-adrenoceptor agonist phenylephrine. This study therefore assessed phenylephrine's selectivity at vascular alpha-adrenoceptors and the mechanism(s) underlying dilation to rauwolscine. EXPERIMENTAL APPROACH: Mouse isolated tail arteries were assessed using a pressure myograph. KEY RESULTS: The alpha(2)-adrenoceptor agonist UK14,304 caused low-maximum constriction that was inhibited by rauwolscine (3 x 10(-8) M) but not by the selective alpha(1)-adrenoceptor antagonist prazosin (10(-7) M). Concentration-effect curves to phenylephrine, cirazoline or noradrenaline were unaffected by rauwolscine but were inhibited by prazosin, which was more effective at high compared with low levels of constriction. In the presence of prazosin, rauwolscine inhibited the curves and was more effective at low compared with high levels of constriction. Although rauwolscine alone did not affect concentration-effect curves to phenylephrine, noradrenaline or cirazoline, it caused marked transient dilation when administered during constriction to these agonists. Dilation was mimicked by another alpha(2)-adrenoceptor antagonist (RX821002, 3 x 10(-8) M), was dependent on agonist selectivity, and did not occur during adrenoceptor-independent constriction (U46619). During constriction to UK14,304 plus U46619, rauwolscine or rapid removal of UK14,304 caused transient dilation that virtually abolished the combined constriction. Endothelial denudation reduced these dilator responses. CONCLUSIONS AND IMPLICATIONS: Inhibition of alpha(2)-adrenoceptors caused transient dilation that was substantially greater than the contribution of alpha(2)-adrenoceptors to the constriction. This reflects a slowly reversing alpha(2)-adrenoceptor-mediated endothelium-dependent dilation and provides a rapid, sensitive test of alpha(2)-adrenoceptor activity. This approach also clearly emphasizes the poor selectivity of phenylephrine at vascular alpha-adrenoceptors. [Description provided by NIOSH]
• Subjects:
  Blood Cardiovascular System Laboratories Nervous System Occupational Health Safety
• Keywords:
  Alpha2-adrenoceptors Author Keywords: Alpha1-adrenoceptors Blood-vessels Cell-biology Cell-differentiation Cell-function Cell-transformation Cirazoline Circulatory-system Endothelium Laboratory-animals Laboratory-testing Muscle-cells Nerve-function Nerves Phenylephrine

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• ISSN:
  0007-1188
• 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:
  158
• Issue:
  5
• NIOSHTIC Number:
  nn:20036435
• Citation:
  Br J Pharmacol 2009 Nov; 158(5):1344-1355
• Contact Point Address:
  Nicholas A Flavahan, Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, Ross Research Building, Room 370, 720 Rutland Ave, Baltimore, MD 21205
• Email:
  nflavah1@jhmi.edu
• Federal Fiscal Year:
  2010
• NORA Priority Area:
  Construction ; Manufacturing
• Performing Organization:
  Johns Hopkins University
• Peer Reviewed:
  True
• Start Date:
  20050801
• Source Full Name:
  British Journal of Pharmacology
• End Date:
  20100731
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:f3f99f044c97a9135290c33895df2e17cc215e3a1f00d256704850ae812a7b6f26bacf276633421207d7f21d13d0468cf71f08b12f35a6e372d2d476bddff804
• Download URL:
  https://stacks.cdc.gov/view/cdc/187866/cdc_187866_DS1.pdf
• File Type:
  [PDF - 796.97 KB ]