V1a vasopressin receptors maintain normal blood pressure by regulating circulating blood volume and baroreflex sensitivity
V1a vasopressin receptors maintain normal blood pressure by regulating circulating blood volume and baroreflex sensitivity
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DOI：
10.1073/pnas.0600875103
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发表时间：
2006-05-16
影响因子：
11.1
通讯作者：
Tsujimoto, Gozoh
中科院分区：
文献类型：
--
作者：
Koshimizu, Taka-aki;Nasa, Yoshihisa;Tsujimoto, Gozoh
精氨酸加压素(AVP)是一种对渗透压和心血管稳态都是必需的激素，通过V1a、V1b和V2三种不同的受体发挥重要的生理调节作用。虽然AVP在临床上被用作循环休克患者的一种有效的血管收缩药(V1a受体介导)，但血管加压素V1a受体在血压稳态中的生理作用尚不清楚。在这项研究中，我们利用基因打靶技术研究了V1a受体在心血管内稳态中的功能作用。与野生型小鼠(V1a(+/+))相比，缺乏V1a受体基因的清醒突变小鼠(V1a(-/-))的基础血压显著降低(P<；0.001)，心率没有明显变化。经超声心动图评估，突变小鼠的心功能没有明显改变。AVP诱导的升压反应在突变小鼠中被取消；相反，AVP导致血压下降，这部分是通过V2受体介导的血管内皮细胞释放一氧化氮发生的。动脉压力感受器反射在突变小鼠中显著受损，这与压力感受性反射控制中心区域的V1a受体丢失一致。值得注意的是，突变小鼠的循环血容量显著减少了9%。此外，突变小鼠的血浆AVP水平和AVP分泌反应正常，但肾上腺皮质对促肾上腺皮质激素的反应显著降低。这些结果表明，V1a受体主要通过调节循环血容量和压力反射敏感性，在正常静息动脉血压调节中发挥重要作用。
Arginine-vasopressin (AVP) is a hormone that is essential for both osmotic and cardiovascular homeostasis, and exerts important physiological regulation through three distinct receptors, V1a, V1b, and V2. Although AVP is used clinically as a potent vasoconstrictor (V1a receptor-mediated) in patients with circulatory shock, the physiological role of vasopressin V1a receptors in blood pressure (BP) homeostasis is ill-defined. In this study, we investigated the functional roles of the V1a receptor in cardiovascular homeostasis using gene targeting. The basal BP of conscious mutant mice lacking the V1a receptor gene (V1a(-/-)) was significantly (P < 0.001) lower compared to the wild-type mice (V1a(+/+)) without a notable change in heart rate. There was no significant alteration in cardiac functions as assessed by echocardiogram in the mutant mice. AVP-induced vasopressor responses were abolished in the mutant mice; rather, AVP caused a decrease in BP, which occurred in part through V2 receptor-mediated release of nitric oxide from the vascular endothelium. Arterial baroreceptor reflexes were markedly impaired in mutant mice, consistent with a loss of V1a receptors in the central area of baroreflex control. Notably, mutant mice showed a significant 9% reduction in circulating blood volume. Furthermore, mutant mice had normal plasma AVP levels and a normal AVP secretory response, but had significantly lower adrenocortical responsiveness to adrenocorticotropic hormone. Taken together, these results indicate that the V1a receptor plays an important role in normal resting arterial BP regulation mainly by its regulation of circulating blood volume and baroreflex sensitivity.