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The Surprising Pharmacology of Vascular α2‐Adrenoceptors
Author(s) -
Crassous PierreAntoine,
Flavahan Sheila,
Flavahan Nicholas
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.933.5
Subject(s) - rauwolscine , constriction , phenylephrine , agonist , chemistry , antagonist , vascular smooth muscle , vasoconstriction , medicine , dilation (metric space) , endocrinology , pharmacology , receptor , smooth muscle , yohimbine , blood pressure , mathematics , combinatorics
Mouse tail arteries express smooth muscle constrictor α1 and α2‐adrenoceptors (α‐ARs). Although pretreatment with the α2‐AR antagonist rauwolscine (3x10‐8M) does not inhibit constriction to α‐AR agonists cirazoline, phenylephrine or norepinephrine, it causes powerful transient dilation when given during constriction to these agonists. Experiments were performed to analyze the mechanism of this dilation in isolated tail arteries. The transient relaxation to rauwolscine was mimicked by another α2‐AR antagonist (RX821002, 3x10‐8M), was dependent on agonist activity at α2‐ARs (norepinephrine = phenylephrine > cirazoline), and did not occur during AR‐independent constriction to U46619. However, during combined constriction to the α2‐AR agonist UK14304 plus U46619, rauwolscine abolished the α2‐AR‐component and caused a powerful transient dilation of the U46619‐component of constriction. A similar dilation was observed after rapid removal of UK14304 from the perfusate. Endothelial denudation abolished these dilator responses. In conclusion, α2‐AR activation is associated with arterial constriction that reverses rapidly, and endothelium‐dependent dilation that reverses slowly. α2‐AR antagonists therefore cause transient dilation that is greater than the contribution of α2‐ARs to the constriction. This interesting phenomenon provides a rapid and sensitive test of agonist selectivity.