ET(B) receptor-deficient rats exhibit reduced contraction to ET-1 despite an increase in ET(A) receptors.
ET(B) receptor-deficient rats exhibit reduced contraction to ET-1 despite an increase in ET(A) receptors.
复制标题
尽管 ET(A) 受体增加，但 ET(B) 受体缺陷的大鼠表现出对 ET-1 的收缩减少。
DOI：
10.1152/ajpheart.2001.281.6.h2680
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发表时间：
2001
期刊：
影响因子：
--
通讯作者：
Fuchs,LC
中科院分区：
文献类型：
--
作者：
Perry,MG;Molero,MM;Giulumian,AD;Katakam,PV;Pollock,JS;Pollock,DM;Fuchs,LC
Several disease states, including hypertension, are associated with elevations in plasma endothelin-1 (ET-1) and variable changes in vascular contraction to ET-1. The spotting lethal (sl) rat carries a deletion of the endothelin-B (ETB) receptor gene that prevents expression of functional ETBreceptors, resulting in elevated plasma ET-1. On a normal diet, these rats are normotensive and thus provide an opportunity to study the vascular effects of chronically elevated ET-1 in the absence of hypertension. Studies were performed in rats homozygous for the ETBdeficiency (sl/sl;n= 8) and in transgenic rats heterozygous for the ETBdeficiency (sl/+;n= 8). Plasma ET-1 was elevated insl/slrats (3.85 ± 0.55 pg/ml) compared withsl/+ rats (0.31 ± 0.11 pg/ml). Mean arterial blood pressure in conscious unrestrainedsl/slandsl/+ rats was 101 ± 5 and 107 ± 6 mmHg, respectively. Concentration-dependent contractions to ET-1 (10−11–10−8M) were reduced in mesenteric small arteries (150–250 μm) fromsl/slrats, as indicated by an ∼10-fold increase in EC50. A selective ETAantagonist, A-127722 (30 nM), abolished contraction to ET-1 in both groups, whereas a selective ETBantagonist had no effect. Also, ETBagonists (IRL-1620 and sarafatoxin 6c) produced neither contraction nor relaxation in either group, indicating that contraction to ET-1 in this vascular segment was exclusively ETAdependent. Despite increased plasma ET-1, protein expression of ETAreceptors in membrane protein isolated from mesenteric small arteries was increased insl/slcompared withsl/+ rats, as shown by Western blotting. These results indicate that, in ETB-deficient rats, ETA-induced contraction is reduced in vessels normally lacking ETB-mediated effects. Reduced contraction may be related to elevated plasma ET-1 and occurs in the presence of increased ETAreceptor protein expression, suggesting an uncoupling of ETAreceptor expression from functional activity.
