Therapeutic potential of atrial natriuretic peptide administration on peripheral arterial diseases
Therapeutic potential of atrial natriuretic peptide administration on peripheral arterial diseases
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DOI：
10.1210/en.2007-1094
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发表时间：
2008-02-01
期刊：
影响因子：
4.8
通讯作者：
Nakao, Kazuwa
中科院分区：
文献类型：
--
作者：
Park, Kwijun;Itoh, Hiroshi;Nakao, Kazuwa
周围动脉疾病是由动脉硬化和侧支血管形成受损引起的，糖尿病会加剧这种疾病，常常导致腿部截肢。我们报道了利钠肽/cGMP/cGMP依赖性蛋白激酶途径的激活加速了小鼠腿部的血管再生和血流恢复，作为外周动脉疾病的模型，通过股动脉结扎诱导了缺血。在这项研究中，腹腔注射卡培肽（一种人重组心房钠尿肽）不仅在非糖尿病小鼠中，而且在链脲佐菌素诱导的高血糖持续16周的小鼠中，通过增加缺血腿部的毛细血管密度来加速血流恢复，与非糖尿病小鼠相比，这显着损害了血流恢复。基于这些发现，我们尝试将卡培立肽给药应用于外周动脉疾病的治疗。该研究组由 13 名患有外周动脉疾病的患者组成（Fontaine 分类为 I，1 例；II，5 例；III，2 例；IV，5 例），常规治疗尚未取得明显效果。 Fontaine 的 I-III 级患者连续静脉注射卡培肽 2 周，IV 级患者静脉注射 4 周。逐渐增加剂量至最大剂量，使患者的收缩压保持在100毫米汞柱以上。卡培肽给药可改善踝臂压力指数、间歇性跛行、静息痛和溃疡。总之，这项研究显示了卡培立肽治疗常规疗法难治的外周动脉疾病的治疗潜力。
Peripheral arterial diseases are caused by arterial sclerosis and impaired collateral vessel formation, which are exacerbated by diabetes, often leading to leg amputation. We have reported that an activation of the natriuretic peptides/cGMP/cGMP-dependent protein kinase pathway accelerated vascular regeneration and blood flow recovery in murine legs, for which ischemia had been induced by a femoral arterial ligation as a model for peripheral arterial diseases. In this study, ip injection of carperitide, a human recombinant atrial natriuretic peptide, accelerated blood flow recovery with increasing capillary density in ischemic legs not only in nondiabetic mice but also in mice kept upon streptozotocin-induced hyperglycemia for 16 wk, which significantly impaired the blood flow recovery compared with nondiabetic mice. Based on these findings, we tried to apply the administration of carperitide to the treatment of peripheral arterial diseases. The study group comprised a continuous series of 13 patients with peripheral arterial diseases ( Fontaine's classification I, one; II, five; III, two; and IV, five), for whom conventional therapies had not accomplished appreciable results. Carperitide was administrated continuously and intravenously for 2 wk to Fontaine's class I-III patients and for 4 weeks to class IV patients. The dose was gradually increased to the maximum, with the patient's systolic blood pressure being kept above 100 mm Hg. Carperitide administration improved the ankle-brachial pressure index, intermittent claudication, rest pain, and ulcers. In conclusion, this study showed a therapeutic potential of carperitide to treat peripheral arterial diseases refractory to conventional therapies.