心房利钠肽诱导猪肾动脉舒张的机制。

The mechanism of relaxation induced by atrial natriuretic peptide in the porcine renal artery.

作者信息

Seguchi H, Nishimura J, Toyofuku K, Kobayashi S, Kumazawa J, Kanaide H

机构信息

Division of Molecular Cardiology, Faculty of Medicine, Kyushu University, Fukuoka, Japan.

出版信息

Br J Pharmacol. 1996 May;118(2):343-51. doi: 10.1111/j.1476-5381.1996.tb15408.x.

DOI:10.1111/j.1476-5381.1996.tb15408.x

PMID:8735636

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1909626/

Abstract

The mechanisms underlying the relaxation of the porcine renal artery induced by atrial natriuretic peptide (ANP) were investigated, using front-surface fluorimetry with fura-2 and receptor-coupled permeabilization by alpha-toxin. 2. ANP decreased the cytosolic Ca2+ concentration ([Ca2+]i) and tension during the contraction induced by a high external K+ solution, in a concentration-dependent manner. This ANP-induced decrease in [Ca2+]i during the contraction induced by high K+ solution was composed of two phases, an initial rapid phase, followed by a maintenance phase. The initial rapid decrease in [Ca2+]i, but not the maintained decrease in [Ca2+]i, was inhibited when the tissue was treated with thapsigargin, a selective Ca2+ pump inhibitor of the sarcoplasmic reticulum. When the tissues were treated with thapsigargin and external Ca2+ was replaced by Ba2+, which cannot be transported by the Ca2+ pump, ANP did not induce a decrease in [Ba2+]i, even though the elevation of tension induced by Ba2+ was strongly inhibited. 3. In the absence of extracellular Ca2+, ANP inhibited the release of Ca2+ from the intracellular store induced by noradrenaline (NA). 4. The [Ca2+]i (abscissa scale)-tension (ordinate scale) relationship observed during the contraction induced by various concentrations of high external K+ solution was shifted downwards by the addition of 10(-8) M ANP, indicating that, at any given [Ca2+]i, the tension generated by high K+ solution was considerably inhibited by the addition of 10(-8) M ANP. The [Ca2+]i-tension curve of the contraction obtained by the cumulative application of external Ca2+ (0-3.75 mM) during depolarization with 118 mM K+ solution was shifted to the left by 3 x 10(-7) M NA. This NA-induced [Ca2+]i-tension relationship was shifted to the right by 10(-8) M ANP, indicating that the ANP-induced reduction of Ca(2+)-sensitivity operates during the contraction induced by NA. 5. In alpha-toxin-permeabilized preparations, ANP induced relaxation of tissues precontracted with a mixture of 3 x 10(-7) M Ca2+, 10(-5) M guanosine 5'-triphosphate (GTP) and 10(-6) M NA. Thus a component of ANP-induced relaxation took place by way of a reduction in the Ca2+ sensitivity of the myofilaments, independent of changes in [Ca2+]i. 6. These results indicate that ANP induces relaxation of the porcine renal artery by: (1) reducing [Ca2+]i mainly via the activation of the Ca2+ pumps located on the sarcoplasmic reticulum and sarcolemma, as well as via inhibition of agoinist-induced release of Ca2+ from the intracellular store; and (2) decreasing the Ca(2+)-sensitivity of the contractile elements.

摘要

采用fura - 2前表面荧光法和α - 毒素受体偶联通透法，研究了心房利钠肽（ANP）诱导猪肾动脉舒张的机制。2. ANP以浓度依赖的方式降低高钾溶液诱导收缩过程中的胞质Ca²⁺浓度（[Ca²⁺]i）和张力。ANP在高钾溶液诱导收缩过程中引起的[Ca²⁺]i降低分为两个阶段，一个初始快速阶段，随后是一个维持阶段。当用毒胡萝卜素（一种肌浆网选择性Ca²⁺泵抑制剂）处理组织时，[Ca²⁺]i的初始快速降低受到抑制，但[Ca²⁺]i的持续降低不受影响。当用毒胡萝卜素处理组织且细胞外Ca²⁺被Ba²⁺替代（Ca²⁺泵不能转运Ba²⁺）时，即使Ba²⁺诱导的张力升高受到强烈抑制，ANP也不会引起[Ba²⁺]i降低。3. 在无细胞外Ca²⁺的情况下，ANP抑制去甲肾上腺素（NA）诱导的细胞内钙库Ca²⁺释放。4. 在不同浓度高钾溶液诱导收缩过程中观察到的[Ca²⁺]i（横坐标）-张力（纵坐标）关系，在加入10⁻⁸M ANP后向下移动，表明在任何给定的[Ca²⁺]i下，加入10⁻⁸M ANP可显著抑制高钾溶液产生的张力。在用118mM钾溶液去极化期间通过累积加入细胞外Ca²⁺（0 - 3.75mM）获得的收缩的[Ca²⁺]i - 张力曲线，在加入3×10⁻⁷M NA后向左移动。这种NA诱导的[Ca²⁺]i - 张力关系在加入10⁻⁸M ANP后向右移动，表明ANP诱导的Ca²⁺敏感性降低在NA诱导的收缩过程中起作用。5. 在α - 毒素通透的制剂中，ANP诱导预先用3×10⁻⁷M Ca²⁺、10⁻⁵M鸟苷5'-三磷酸（GTP）和10⁻⁶M NA混合物预收缩的组织舒张。因此，ANP诱导舒张的一个成分是通过降低肌丝的Ca²⁺敏感性发生的，与[Ca²⁺]i的变化无关。6. 这些结果表明，ANP通过以下方式诱导猪肾动脉舒张：（1）主要通过激活位于肌浆网和肌膜上的Ca²⁺泵以及抑制激动剂诱导的细胞内钙库Ca²⁺释放来降低[Ca²⁺]i；（2）降低收缩成分的Ca²⁺敏感性。