Reduced sickle erythrocyte dehydration in vivo by endothelin-1 receptor antagonists.

Reduced sickle erythrocyte dehydration in vivo by endothelin-1 receptor antagonists. Research Abstract Details 

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Reduced sickle erythrocyte dehydration in vivo by endothelin-1 receptor antagonists. Abstract Text:

Alicia Rivera,

Elevated plasma levels of cytokines such as endothelin-1 (ET-1) have been shown to be associated with sickle cell disease (SCD). However, the role of ET-1 in the pathophysiology of SCD is not entirely clear. I now show that treatment of SAD mice, a transgenic mouse model of SCD, with BQ-788 (0.33 mg.kg(-1).day(-1) intraperitoneally for 14 days), an ET-1 receptor B (ET(B)) antagonist, induced a significant decrease in Gardos channel activity (1.7 +/- 0.1 to 1.0 +/- 0.4 mmol.10(13) cell(-1).h(-1), n = 3, P = 0.019) and reduced the erythrocyte density profile by decreasing the mean density (D(50); n = 4, P = 0.012). These effects were not observed in mice treated with BQ-123, an ET-1 receptor A (ET(A)) antagonist. A mixture of both antagonists induced a similar change in density profile as with BQ-788 alone that was associated with an increase in mean cellular volume and a decrease in corpuscular hemoglobin concentration mean. I also observed in vitro effects of ET-1 on human sickle erythrocyte dehydration that was blocked by BQ-788 and a mixture of ET(B)/ET(A) antagonists but not by ET(A) antagonist alone. These results show that erythrocyte hydration status in vivo is mediated via activation of the ET(B) receptor, leading to Gardos channel modulation in SCD.

Reduced sickle erythrocyte dehydration in vivo by endothelin-1 receptor antagonists. Publishing Authors By Initials

A Rivera,

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Reduced sickle erythrocyte dehydration in vivo by endothelin-1 receptor antagonists. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: American journal of physiology. Cell physiology

VOLUME: 293

Page Numbers: C960-6

Journal Abbreviation: Am. J. Physiol., Cell Physiol.

ISSN: 0363-6143

DAY: 9

MONTH: 05

YEAR: 2007

Reduced sickle erythrocyte dehydration in vivo by endothelin-1 receptor antagonists. Information

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LANGUAGE: eng

NlmUniqueID: 100901225

Reduced sickle erythrocyte dehydration in vivo by endothelin-1 receptor antagonists. Keywords Mesh Terms:

KEYWORDS: Water

MESH TERMS: metabolism

Chemical & Substance for Abstract: Reduced sickle erythrocyte dehydration in vivo by endothelin-1 receptor antagonists. Information

Substance Name: Water

Registry Number: 7732-18-5

Grant and Affiliation Information for Reduced sickle erythrocyte dehydration in vivo by endothelin-1 receptor antagonists.

AFFILIATION: Dept. of Laboratory Medicine, Bader 7, Children's Hospital Boston, 300 Longwood Ave., Boston, MA 02115, USA. alicia.rivera@childrens.harvard.edu

Country: United States

AGENCY: United States NHLBI

GRANT: HL067699

ACRONYM: HL

MEDLINETA: Am J Physiol Cell Physiol

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