Endothelin-1 and endothelin receptor status in kidney transplants undergoing acute rejection

Obesity is associated with dysregulation of the endothelin system. In obese individuals, an exaggerated pressor response to acute stress is accompanied by increased circulating endothelin-1. The impact of combined endothelin A/B receptor (ETA/B) antagonism on the stress-induced pressor response in overweight/obese individuals is unknown. Objective: To test the hypothesis that treatment with an ETA/B antagonist (bosentan) would reduce the stress-induced pressor response and arterial stiffness in overweight/obese compared to normal weight individuals. Methods: 40 participants [Normal weight (NW): n=20, BMI: 21.7 ± 2.4 kg/m2 & Overweight/obese (OB): n=20, BMI: 33.8 ± 8.2 kg/m2] were randomized to placebo or 125 mg of bosentan twice a day (250 mg total) for 3 days. Hemodynamics were assessed before, during, and after a cold pressor test (CPT). Endothelin-1 was assessed at baseline and immediately after CPT. Following a washout period, the same protocol was repeated with the opposite treatment. Results: The change from baseline in mean arterial pressure (MAP) during CPT following bosentan was significantly lower (p=0.039) in the OB group, compared to the NW group (OB: 28±12 vs LN: 34±15 mm Hg). Conclusions: These results suggest that ETA/B antagonism favorably blunts the pressor response to acute stress in overweight/obese individuals.

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The significant effect of HLA-DRB1 matching on acute rejection in kidney transplants

Transplant International ◽

10.1007/978-3-662-00818-8_4 ◽

1996 ◽

pp. 11-15

Author(s):

Michio Nojima ◽

Hideari Ihara ◽

Masahiro Kyo ◽

Mitsuo Hashimoto ◽

Kiichiro Ito ◽

...

Keyword(s):

Acute Rejection ◽

Kidney Transplants

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Biotinyl Endothelin-1 Binding to Endothelin Receptor and its Applications

Journal of Cardiovascular Pharmacology ◽

10.1097/01.fjc.0000132316.24513.ec ◽

2004 ◽

Vol 44 (3) ◽

pp. 287-293 ◽

Cited By ~ 3

Author(s):

K Saravanan ◽

M Paramasivam ◽

S Dey ◽

T P Singh ◽

A Srinivasan

Keyword(s):

Endothelin Receptor ◽

Endothelin 1

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Sarcoplasmic-endoplasmic reticulum Ca2+-ATPase inhibition prevents endothelin A receptor antagonism in rat aorta

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00298.2006 ◽

2007 ◽

Vol 292 (4) ◽

pp. H1961-H1966 ◽

Cited By ~ 6

Author(s):

M. Tosun ◽

Y. Erac ◽

C. Selli ◽

N. Karakaya

Keyword(s):

Endoplasmic Reticulum ◽

Receptor Antagonist ◽

Cyclopiazonic Acid ◽

Rat Aorta ◽

Endothelin Receptor Antagonist ◽

Endothelin Receptor ◽

Atpase Inhibitor ◽

Endothelin 1 ◽

Endothelin A Receptor ◽

Endothelin A

This study tested whether sarcoplasmic-endoplasmic reticulum Ca2+-ATPase regulates the ability of endothelin receptor antagonist to inhibit the endothelin-1 constriction. The endothelin A receptor antagonist BQ-123 (1 μM) completely relaxed constriction to 10 nM endothelin-1 in endothelium-denuded rat aorta. Challenge with cyclopiazonic acid (10 μM), a sarcoplasmic-endoplasmic reticulum Ca2+-ATPase inhibitor, during the plateau of endothelin-1 constriction enhanced the constriction by ∼30%. BQ-123 relaxed the endothelin-1 plus cyclopiazonic acid constriction by only ∼10%. In contrast, prazosin (1 μM), an α-adrenergic receptor antagonist, still completely relaxed the 0.3 μM phenylephrine constriction in the presence of cyclopiazonic acid. Verapamil relaxed the endothelin-1 plus cyclopiazonic acid constriction by ∼30%, whereas Ni2+ and 2-aminoethoxydiphenyl borate, nonselective cation channel and store-operated channel blockers, respectively, completely relaxed the constriction. These results suggest that lowered sarcoplasmic-endoplasmic reticulum Ca2+-ATPase activity selectively decreases the ability of endothelin receptor antagonist to inhibit the endothelin A receptor. The decreased antagonism may be related to the opening of store-operated channels and subsequent greater internalization of endothelin A receptor.

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