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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Adrenomedullin gene expression differences in mice do not affect blood pressure but modulate hypertension-induced pathology in males
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Adrenomedullin gene expression differences in mice do not affect blood pressure but modulate hypertension-induced pathology in males

机译：小鼠肾上腺髓质素基因表达差异不会影响血压，但会调节男性高血压引起的病理

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摘要

Adrenomedullin (AM) is a potent vasodilator peptide in plasma at picomolar levels. Polymorphisms in the human AM gene have been associated with genetic predisposition to diabetic nephropathy and proteinuria with essential hypertension, and numerous studies have demonstrated that endogenous AM plays a role in protecting the heart and kidneys from fibrosis resulting from cardiovascular disease. Elevated plasma levels of AM are associated with pregnancy and sepsis and with cardiovascular stress and hypertension. However, there are no reports of the effects of genetic differences in the expression of the endogenous AM gene and of gender on blood pressure in these circumstances or on the pathological changes accompanying hypertension. To address these questions, we have generated mice having genetically controlled levels of AM mRNA ranging from ≈ 50% to ≈ 140% of wild-type levels. These modest changes in AM gene expression have no effect on basal blood pressure. Although pregnancy and sepsis increase plasma AM levels, genetically reducing AM production does not affect the transient hypotension that occurs during normal pregnancy or that is induced by treatment with lipopolysaccharide. Nor does the reduction of AM affect chronic hypertension caused by a renin transgene. However, 50% normal expression of AM enhances cardiac hypertrophy and renal damage in male, but not female, mice with a renin transgene. These observations suggest that the effect of gender on the role of AM in counteracting cardiovascular damage in humans merits careful evaluation.
机译：肾上腺髓质素（AM）是血浆中皮摩尔水平的有效血管扩张肽。人类AM基因的多态性与糖尿病肾病和蛋白尿伴原发性高血压的遗传易感性有关，许多研究表明内源性AM在保护心脏和肾脏免受心血管疾病引起的纤维化的作用。 AM的血浆水平升高与妊娠和败血症以及心血管压力和高血压有关。然而，在这些情况下，没有内源性AM基因表达的性别差异和性别对血压的影响，也没有关于高血压所致病理变化的报道。为了解决这些问题，我们已经产生了具有基因控制水平的AM mRNA的小鼠，其野生型水平的范围从≈50％到≈140％。 AM基因表达的这些适度变化对基础血压没有影响。尽管妊娠和脓毒症会增加血浆AM水平，但从基因上降低AM产生量并不会影响正常妊娠期间发生的暂时性低血压或由脂多糖治疗引起的短暂性低血压。 AM的降低也不影响由肾素转基因引起的慢性高血压。但是，AM的50％正常表达会增强具有肾素转基因的雄性（而非雌性）小鼠的心脏肥大和肾脏损害。这些观察结果表明，性别对AM在抵抗人类心血管损伤中的作用的影响值得仔细评估。

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