BOTH ET(A) AND ET(B) RECEPTORS MEDIATE CONTRACTION TO ENDOTHELIN-1 IN HUMAN BLOOD-VESSELS

被引:468
作者
SEO, B
OEMAR, BS
SIEBENMANN, R
VONSEGESSER, L
LUSCHER, TF
机构
[1] UNIV HOSP BASEL,DEPT RES,CH-4031 BASEL,SWITZERLAND
[2] UNIV HOSP BASEL,DEPT MED,CH-4031 BASEL,SWITZERLAND
[3] UNIV HOSP BERN,DEPT RES,CH-3010 BERN,SWITZERLAND
[4] UNIV HOSP BERN,DEPT MED,CH-3010 BERN,SWITZERLAND
[5] HEART CTR,HIRSLANDEN,SWITZERLAND
[6] UNIV HOSP ZURICH,DEPT SURG,CH-8091 ZURICH,SWITZERLAND
[7] GYEONGSANG NATL UNIV HOSP,DEPT MED,CHINJU,SOUTH KOREA
关键词
ARTERIES; VEINS; ENDOTHELIN;
D O I
10.1161/01.CIR.89.3.1203
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background Endothelin (ET)-1 has potent vascular effects. Two endothelin receptors have been cloned, namely, the ET(A) receptor, which preferentially binds ET-1, and the ET(B) receptor, which equally binds ET-1 and ET-3 and preferentially sarafotoxin S6c. We characterized endothelin receptor subtypes on vascular smooth muscle and endothelium of isolated human internal mammary artery (IMA) and vein (IMV) and porcine coronary artery (PCA) using the ET(A) antagonists FR139317 and BQ-123, the ET(B) ligand sarafotoxin S6c, and the ET(A)/ET(B) antagonist Ro 47-0203 (bosentan). Methods and Results In endothelium-denuded IMA and PCA and less so in IMV, FR139317 and BQ-123 (in PCA only) shifted the concentration-contraction curves to ET-1 parallel to the right. However, even at 10(-5) mol/L, FR139317 did not inhibit a high-sensitivity portion of the concentration-contraction curve. Moreover, the ET(B) receptor agonist sarafotoxin S6c induced contraction in vessels preincubated with FR139317. IMV was significantly more sensitive to the contractile effect of ET-1 and sarafotoxin S6c than was IMA (P<.05). Prolonged incubation with sarafotoxin S6c (to downregulate ET(B) receptors) and FR139317 eliminated the contraction resistant to FR139317. The ET(A)/ET(B) receptor antagonist bosentan caused a parallel shift of the concentration-contraction curve to the right at all concentrations of endothelin. ET(B) receptor mRNA was detected by Northern blot analysis in IMA and aortic smooth muscle cells. In precontracted IMA and PCA with endothelium, sarafotoxin S6c did not cause endothelium-dependent relaxations, whereas transient responses occurred in IMV. Conclusions Vascular smooth muscle cells of human IMA, IMV, and PCA contain both ET(A) and ET(B) receptors, whereas the endothelium of IMA and PCA does not express functional ET(B) receptors linked to nitric oxide and/or prostacyclin production. Hence, inhibition of endothelin-induced contraction in patients requires the use of combined ET(A)/ET(B) antagonists.
引用
收藏
页码:1203 / 1208
页数:6
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