Sympathy for the devil: the role of thromboxane in the regulation of vascular tone and blood pressure.
Sympathy for the devil: the role of thromboxane in the regulation of vascular tone and blood pressure.
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DOI：
10.1152/ajpheart.01318.2007
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发表时间：
2008-05
期刊：
影响因子：
--
通讯作者：
M. Sellers;J. Stallone
中科院分区：
文献类型：
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作者：
M. Sellers;J. Stallone
从历史上看，血管舒张性前列腺素类，尤其是前列环素和前列腺素E（2），被认为主要通过抵消全身血管收缩系统（包括血管紧张素II、儿茶酚胺和加压素）的主要作用，对正常血管张力和血压（BP）的调节有重要作用。相反，在正常状态下，初级血管收缩剂前列腺素类血栓素A（2）（TxA（2））的产生量要小得多。虽然TxA（2）被认为在各种心血管疾病中起重要作用，如心肌梗死、脑血管痉挛、高血压、先兆子痫和各种血栓性疾病，但其在正常生理状态下调节血管张力和血压的作用充其量是不确定的。许多研究已经坚定地建立了这样一个教条：TxA（2）虽然在男性的病理生理状态中很重要，但在女性的血管张力或血压调节中几乎没有作用，除了在肺血管中。然而，这一概念在很大程度上是基于动物和人类研究中雄性动物的主要和优先使用。我们实验室和其他人最近的研究挑战了这一教条，并揭示了全身血管壁中的TxA（2）通路是一种雌激素依赖性机制，在正常和病理生理状态下女性血管张力和血压的调节中发挥重要作用。研究表明，TxA（2）的强有力的血管收缩作用对正常状态下的女性是有益的，它作为一种局部反调节机制，增加血管张力和血压，并防止可能由女性血管壁中存在的多种雌激素敏感的局部血管舒张机制引起的低血压。验证这一建议必须等待进一步的研究，在系统，组织和分子水平。
Historically, the vasodilatory prostanoids, especially prostacyclin and prostaglandin E(2), are believed to contribute significantly to the regulation of normal vascular tone and blood pressure (BP), primarily by counteracting the prevailing effects of the systemic vasoconstrictor systems, including angiotensin II, the catecholamines, and vasopressin. In contrast, the primary vasoconstrictor prostanoid thromboxane A(2) (TxA(2)) is produced in far smaller quantities in the normal state. While TxA(2) is believed to play a significant role in a variety of cardiovascular diseases, such as myocardial infarction, cerebral vasospasm, hypertension, preeclampsia, and various thrombotic disorders, its role in the regulation of vascular tone and BP in the normal physiological state is, at best, uncertain. Numerous studies have firmly established the dogma that TxA(2), while important in pathophysiological states in males, plays little or no role in the regulation of vascular tone or BP in females, except in the pulmonary vasculature. However, this concept is largely based on the predominant and preferential use of males in animal and human studies. Recent studies from our laboratory and others challenge this dogma and reveal that the TxA(2) pathway in the systemic vascular wall is an estrogen-dependent mechanism that appears to play an important role in the regulation of vascular tone and BP in females, in both normal and pathophysiological states. It is proposed that the potent vasoconstrictor action of TxA(2) is beneficial in the female in the normal state by acting as a local counterregulatory mechanism to increase vascular tone and BP and defend against hypotension that could result from the multiple estrogen-sensitive local vasodilator mechanisms present in the female vascular wall. Validation of this proposal must await further studies at the systemic, tissue, and molecular levels.