Stingo A J, Clavell A L, Aarhus L L, Burnett J C
Cardiorenal Research Laboratory, Mayo Clinic and Foundation, Rochester, MN 55905.
Hypertension. 1993 Jul;22(1):62-6. doi: 10.1161/01.hyp.22.1.62.
The current study was undertaken to define a biological role for the endothelin-A receptor in a clinically relevant model of altered systemic and renal function produced by suprarenal aortic cross-clamping. This model is associated with profound systemic and renal vasoconstriction, acute renal failure, and a significant increase in circulating endothelin. Studies were performed in three groups of anesthetized mongrel dogs. Group 1 (n = 5) underwent aortic cross-clamping for 1 hour; group 2 (n = 5) underwent aortic cross-clamping for 1 hour in the presence of BQ-123, a specific antagonist of the endothelin-A receptor; group 3 (n = 4) received BQ-123 alone. The marked systemic and renal vasoconstriction associated with aortic cross-clamping in group 1 was markedly attenuated in group 2 in the presence of BQ-123. Unlike the vasoconstrictor response, BQ-123 did not attenuate the decrease in glomerular filtration rate associated with this model. Under unstimulated conditions in group 3, BQ-123 had no actions on systemic or renal hemodynamics. In conclusion, the current study demonstrates that the systemic and renal vasoconstriction associated with aortic cross-clamping are in part mediated through the interaction of endothelin and the endothelin-A receptor. This study demonstrates the functional importance of increased endogenous endothelin in the regulation of vascular tone in this pathophysiological state.
本研究旨在确定内皮素-A受体在由肾上主动脉交叉钳夹导致的全身和肾功能改变的临床相关模型中的生物学作用。该模型与严重的全身和肾血管收缩、急性肾衰竭以及循环内皮素显著增加有关。研究在三组麻醉的杂种犬中进行。第1组（n = 5）进行主动脉交叉钳夹1小时；第2组（n = 5）在存在内皮素-A受体特异性拮抗剂BQ-123的情况下进行主动脉交叉钳夹1小时；第3组（n = 4）仅接受BQ-123。在BQ-123存在的情况下，第2组中与主动脉交叉钳夹相关的明显的全身和肾血管收缩在第1组中明显减弱。与血管收缩反应不同，BQ-123并未减弱与该模型相关的肾小球滤过率的降低。在第3组的未刺激条件下，BQ-123对全身或肾血流动力学无作用。总之，本研究表明，与主动脉交叉钳夹相关的全身和肾血管收缩部分是通过内皮素与内皮素-A受体的相互作用介导的。本研究证明了内源性内皮素增加在这种病理生理状态下血管张力调节中的功能重要性。
