ROLE OF ENDOTHELIN RECEPTOR SUBTYPES IN THE IN-VIVO REGULATION OF RENAL-FUNCTION
ROLE OF ENDOTHELIN RECEPTOR SUBTYPES IN THE IN-VIVO REGULATION OF RENAL-FUNCTION
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DOI：
10.1152/ajprenal.1995.268.3.f455
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发表时间：
1995-03-01
期刊：
影响因子：
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通讯作者：
BURNETT, JC
中科院分区：
文献类型：
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作者：
CLAVELL, AL;STINGO, AJ;BURNETT, JC
内皮素(ET)是一种内皮来源的强效血管收缩多肽，在低剂量时可引起肾血管收缩和利尿，对钠的排泄有不同的作用。目前在四组麻醉犬中进行的研究旨在确定ET(A)和ET(B)受体亚型在低剂量外源性ET肾脏作用中的作用。第1组(n=4)动物作为时间对照。在第2组(n=6)，静脉注射ET-1(5 ng·kg~(-1)·min(~(-1)可引起肾血管收缩，抗心绞痛，增加近端钠重吸收，利尿，降低尿渗透压。在第3组(n=6)，肾内注射选择性ET(A)拮抗剂BQ-123(4µg·kg~(-1)·min~(-1))，可阻断ET-1引起的肾脏血流动力学改变，并在近端肾小管水平发挥利钠作用。相反，BQ-123不改变ET的利尿反应。在第4组(n=6)，肾内注射选择性ET(B)受体激动剂6-c可引起利尿反应，但不改变钠排泄。这些研究表明，ET(A)受体参与了肾血管收缩，而ET(B)受体在外源性ET的利尿反应中起主要作用。这项研究还表明，在低剂量下，ET通过减少近端肾小管对钠的重吸收而在体内发挥利钠作用，而不依赖于ET(A)或ET(B)受体的激活。
Endothelin (ET) is a potent vasoconstrictor peptide of endothelial origin, which at low doses results in renal vasoconstriction and diuresis with variable actions on sodium excretion. The current study conducted in four groups of anesthetized dogs was designed to define the role of the ET(A) and ET(B) receptor subtypes in the renal actions of low-dose exogenous ET. Group 1 (n = 4) animals served as time controls. In group 2 (n = 6) a systemic ET-1 (5 ng.kg(-1).min(-1)) infusion mediated renal vasoconstriction, antinatriuresis with increases in proximal fractional reabsorption of sodium, and diuresis with a decrease in urine osmolality. In group 3 (n = 6) intrarenal BQ-123 (4 mu g kg(-1) min(-1)), a selective ET(A) antagonist, abolished the systemic ET-1-mediated changes in renal hemodynamics and unmasked a natriuretic action at the level of the proximal tubule. In contrast, the diuretic response of ET was not altered by BQ-123. In group 4 (n = 6) intrarenal sarafotoxin 6-c, a selective ET(B) receptor agonist, resulted in a diuretic response without a change in sodium excretion. These studies suggest that the ET(A) receptor contributes to the renal vasoconstriction, whereas the ET(B) receptor is largely responsible for the diuretic response during exogenous ET. This study also suggests that at low doses ET is natriuretic in vivo by decreasing proximal tubular reabsorption of sodium independent of ET(A) or ET(B) receptor activation.