TY - JOUR
T1 - Selective enhancement of contractions to α1-adrenergic receptor activation in the aorta of mice with sickle cell disease
AU - Juncos, Ramiro
AU - Juncos, Luis
AU - Hebbel, Robert P.
AU - Vercellotti, Gregory M.
AU - Katusic, Zvonimir S.
AU - Nath, Karl A.
PY - 2011/2
Y1 - 2011/2
N2 - 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.
AB - 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.
KW - a1-adrenergic receptors
KW - phenylephrine
KW - sickle cell disease
KW - vascular reactivity
KW - vasoconstriction
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U2 - 10.1097/FJC.0b013e318204bb34
DO - 10.1097/FJC.0b013e318204bb34
M3 - Article
C2 - 21107280
AN - SCOPUS:78851469077
SN - 0160-2446
VL - 57
SP - 263
EP - 266
JO - Journal of Cardiovascular Pharmacology
JF - Journal of Cardiovascular Pharmacology
IS - 2
ER -