Selective enhancement of contractions to α1-adrenergic receptor activation in the aorta of mice with sickle cell disease

Ramiro Juncos, Luis Juncos, Robert P. Hebbel, Gregory M. Vercellotti, Zvonimir S. Katusic, Karl A. Nath

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

Sickle cell disease (SCD), the most common inherited hematologic disorder in the United States and the most common single gene disorder in the world, causes substantial morbidity and mortality. The major pathobiologic processes that underlie SCD include vaso-occlusion, inflammation, procoagulant processes, hemolysis, and altered vascular reactivity. The present study examined the vasoactive response to α-adrenergic activation in a murine model of SCD. Isolated aortas from sickle mice as compared with wild-type mice exhibit heightened contractions to norepinephrine and phenylephrine; such responses were completely blocked by an α1-receptor antagonist, prazosin. Aortas from either group exhibited comparable contractile responses to potassium chloride and the thromboxane agonist U46619 and no contractile response to an α2-adrenergic receptor agonist, UK14304. We conclude that there is an exaggerated vasoconstrictive response to α1-receptor agonists in SCD. Because sickle crisis is induced by diverse forms of stress, the latter attended by increased adrenergic activity, our findings may be relevant to the occurrence of sickle crisis. We also suggest that such heightened reactivity may contribute to vaso-occlusive processes that underlie ischemic injury in SCD. Finally, our findings urge caution in the use of phenylephrine in patients with SCD.

Original languageEnglish (US)
Pages (from-to)263-266
Number of pages4
JournalJournal of Cardiovascular Pharmacology
Volume57
Issue number2
DOIs
StatePublished - Feb 2011

Keywords

  • a1-adrenergic receptors
  • phenylephrine
  • sickle cell disease
  • vascular reactivity
  • vasoconstriction

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

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