Arterial remodeling and plasma volume expansion in caveolin-1-deficient mice
Arterial remodeling and plasma volume expansion in caveolin-1-deficient mice
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DOI：
10.1152/ajpregu.00092.2007
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发表时间：
2007-09-01
影响因子：
2.8
通讯作者：
Swaerd, Karl
中科院分区：
文献类型：
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作者：
Albinsson, Sebastian;Shakirova, Yulia;Swaerd, Karl
Caveolin-1 ( Cav-1) 对于膜小窝的形态至关重要，并对许多信号系统产生负面影响，包括一氧化氮 (NO) 的产生和 MAP 激酶级联的活性。因此，在血管系统中，caveolin-1 的消融可能会导致动脉扩张和血管壁质量增加（重塑）。通过对肠系膜阻力动脉进行详细的形态测量和功能分析，在 Cav-1 敲除 (KO) 小鼠中对此进行了测试，显示缺乏小窝。定量形态测量显示 KO 中介质厚度和介质与管腔比率增加。 KO 动脉中压力诱导的肌源性张力和流量诱导的扩张均减少，但在 NO 合酶 (NOS) 抑制后，两者均增加至野生型 (WT) 水平。 NOS抑制后的等长力记录显示KO中被动和主动长度-力关系向右移动，并且对α1-肾上腺素能刺激的力反应增加。相比之下，KO 组与 WT 组相比，主动脉的中膜厚度和力响应没有改变，而管腔直径则有所增加。 KO 与 WT 中异氟醚麻醉期间的平均动脉血压没有差异，但随着时间的推移，血压波动更大。 NOS 抑制后，KO 中的波动消失，压力增加 (38 +/- 6%) 是 WT (17 +/- 3%) 的两倍。示踪剂稀释实验显示 KO 中血浆体积增加。我们得出的结论是，NO 对 Cav-1 KO 小鼠的血压影响比 WT 小鼠更大，并且阻力血管的重组和对肾上腺素能刺激的反应性增加补偿了 Cav-1 KO 小鼠中张力的降低。
Caveolin- 1 ( Cav- 1) is essential for the morphology of membrane caveolae and exerts a negative influence on a number of signaling systems, including nitric oxide ( NO) production and activity of the MAP kinase cascade. In the vascular system, ablation of caveolin- 1 may thus be expected to cause arterial dilatation and increased vessel wall mass ( remodeling). This was tested in Cav- 1 knockout ( KO) mice by a detailed morphometric and functional analysis of mesenteric resistance arteries, shown to lack caveolae. Quantitative morphometry revealed increased media thickness and media- to- lumen ratio in KO. Pressure- induced myogenic tone and flow- induced dilatation were decreased in KO arteries, but both were increased toward wild- type ( WT) levels following NO synthase ( NOS) inhibition. Isometric force recordings following NOS inhibition showed rightward shifts of passive and active length- force relationships in KO, and the force response to alpha 1- adrenergic stimulation was increased. In contrast, media thickness and force response of the aorta were unaltered in KO vs. WT, whereas lumen diameter was increased. Mean arterial blood pressure during isoflurane anesthesia was not different in KO vs. WT, but greater fluctuation in blood pressure over time was noted. Following NOS inhibition, fluctuations disappeared and pressure increased twice as much in KO ( 38 +/- 6%) compared with WT ( 17 +/- 3%). Tracer- dilution experiments showed increased plasma volume in KO. We conclude that NO affects blood pressure more in Cav- 1 KO than in WT mice and that restructuring of resistance vessels and an increased responsiveness to adrenergic stimulation compensate for a decreased tone in Cav- 1 KO mice.