Cardiovascular actions of ET-B activation in vivo and modulation by receptor antagonism

被引:9
作者
Rasmussen, TE
Jougasaki, M
Supaporn, T
Hallett, JW
Brooks, DP
Burnett, JR
机构
[1] Mayo Clin, Cardiorenal Res Lab, Div Cardiovasc Dis, Rochester, MN 55905 USA
[2] Mayo Clin, Cardiorenal Res Lab, Div Vasc Surg, Rochester, MN 55905 USA
[3] Mayo Clin, Dept Internal Med, Rochester, MN 55905 USA
[4] Mayo Clin, Dept Surg, Rochester, MN 55905 USA
[5] SmithKline Beecham, King Of Prussia, PA 19406 USA
关键词
endothelium; sarafotoxin S6c; peptide;
D O I
10.1152/ajpregu.1998.274.1.R131
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
The endothelin (ET)-B receptor subtype is expressed on vascular endothelial and smooth muscle cells and participates in vasodilatation and vasoconstriction. Controversy exists regarding the role of the ET-B receptor as a mediator of systemic, pulmonary, and renal vasoconstriction in states of marked ET-1 activation. Moreover, the potential activation of endogenous ET-1 with secondary stimulation of the ET-A receptor in response to sarafotoxin S6c (S6c) remains unclear. This study was designed to assess the cardiovascular actions of ET-B activation with S6c in the presence and absence of selective ET-A antagonism with FR-139317 and dual ET-A/ET-B antagonism with SE-209670 in the anesthetized dog. Compared with time control (n = 5), S6c increased from baseline systemic vascular resistance (SVR) [28 +/- 7 vs. 14 +/- 3 resistance units (RU), P < 0.05] and pulmonary vascular resistance (PVR) (3.2 +/- 0.7 vs. 0.9 +/- 0.3 RU, P < 0.05) and decreased cardiac output (GO) (-1.7 +/- 0.3 vs. -0.5 +/- 0.1 l/min, P < 0.05), with no differences in renal vascular resistance in association with increases in plasma ET-1. S6c also decreased mixed venous oxygen saturation (Sv(O2)) (56 +/- 6 vs. 76 +/- 5%, P < 0.05). Selective ET-A receptor antagonism did not affect the actions of S6c, with the exception that ET-A receptor antagonism blocked the increase in SVR to high-dose S6c. Dual ET-A/ET-B receptor antagonism attenuated the increase from baseline in SVR (7 +/- 1 vs. 28 +/- 7 RU, P < 0.05) and PVR (0.7 +/- 0.2 vs. 3.2 +/- 0.7 RU, P < 0.05) and decrease from baseline in CO (-0.9 +/- 0.1 vs. -1.7 +/- 0.3 l/min, P < 0.05) and Sv(O2) (-7 +/- 3 vs. -20 +/- 3%, P < 0.05) observed with S6c alone. In summary, this study demonstrates an important role of ET-B receptor activation in vivo, which results in increases in plasma ET-1 and systemic and pulmonary vasoconstriction and reductions in CO and Sv(O2). This study also supports a modest role for the ET-A receptor in mediating the systemic vasoconstrictor response to high-dose S6c.
引用
收藏
页码:R131 / R138
页数:8
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