BACKGROUND AND AIMS Acute intermittent porphyria (AIP) results from a partial deficiency of porphobilinogen deaminase (PBGD). Symptomatic AIP patients, most of whom are women, experience acute attacks characterized by severe abdominal pain and abrupt increases in blood pressure. Here, we characterized the reactivity of mesenteric arteries from male and female AIP mice with ~30% of normal PBGD activity and wild type C57BL/6 mice. METHODS An acute porphyric attack was induced in AIP mice by treatment with phenobarbital. Vascular responses to K+, phenylephrine (PE), acetylcholine (ACh), and hemin were determined (Wire Multi Myograph). RESULTS Maximal contraction to PE was increased in arteries from male and female AIP mice (p < .05) during an induced attack of acute porphyria. Female AIP arteries had increased sensitivity to PE (p < .05) even after nitric oxide (NO) blockade with Nω-nitro-L-arginine methyl ester (L-NAME) (p < .05). Maximal relaxation to ACh was similar in males and females with lower sensitivity in female AIP arteries (p < .05). Hemin induced greater relaxation in AIP arteries in both males and females (p < .05). SUMMARY/CONCLUSIONS Sex differences in this AIP mouse model include a pro-contractile response in females. These alterations may contribute to the increased blood pressure during an acute attack and provide a novel mechanism of action whereby heme ameliorates the attacks.

中文翻译：

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急性间歇性卟啉症小鼠模型的肠系膜动脉血管反应性的性别差异。

背景与目的急性间歇性卟啉症（AIP）是由胆色素原脱氨酶（PBGD）的部分缺乏引起的。有症状的AIP患者（大多数为女性）会遭受急性发作，其特征是严重的腹痛和血压突然升高。在这里，我们表征了约30％正常PBGD活性的雄性和雌性AIP小鼠和野生型C57BL / 6小鼠的肠系膜动脉的反应性。方法苯巴比妥治疗AIP小鼠可引起急性卟啉发作。确定了对K +，去氧肾上腺素（PE），乙酰胆碱（ACh）和血红素的血管反应（Wire Multi Myograph）。结果在急性卟啉症诱发发作期间，雄性和雌性AIP小鼠的动脉对PE的最大收缩增加（p <.05）。女性AIP动脉对PE的敏感性增加（p <。05），甚至在一氧化氮（NO）被Nω-硝基-L-精氨酸甲酯（L-NAME）阻断后（p <.05）。男性和女性对ACh的最大舒张相似，女性AIP动脉的敏感性较低（p <.05）。血红素引起男性和女性的AIP动脉更大的舒张（p <.05）。总结/结论这种AIP小鼠模型的性别差异包括雌性的收缩反应。这些改变可能会导致急性发作期间血压升高，并提供一种新的作用机制，从而使血红素改善发作。血红素引起男性和女性的AIP动脉更大的舒张（p <.05）。总结/结论这种AIP小鼠模型的性别差异包括雌性的收缩反应。这些改变可能会导致急性发作期间血压升高，并提供一种新的作用机制，从而使血红素改善发作。血红素引起男性和女性的AIP动脉更大的舒张（p <.05）。总结/结论这种AIP小鼠模型的性别差异包括雌性的收缩反应。这些改变可能会导致急性发作期间血压升高，并提供一种新的作用机制，从而使血红素改善发作。