Division of Molecular Pharmacology, Department of Pharmacology, Jichi Medical University, 3311-1 Shimotsuke, Yakushiji, Tochigi, 329-0498, Japan.
Clin Exp Nephrol. 2012 Feb;16(1):30-4. doi: 10.1007/s10157-011-0497-y. Epub 2011 Nov 1.
A prompt rise in blood pressure occurs when arginine-vasopressin is administered in quantities adequate to activate vascular V1a subtype vasopressin receptors. However, it has been controversial whether the endogenous vasopressin-V1a system contributes to the maintenance of basal blood pressure during normal development and aging. Mutant mice lacking the V1a receptor gene (V1a(-/-)) show significantly lower blood pressure compared to control mice, without a notable change in heart rate. In V1a(-/-) mice, arterial baroreceptor reflexes were attenuated due to malfunctioning baroreflex center, and the mice's circulating blood volume was significantly reduced. In line with this reduction in circulating blood volume, adrenocortical hormone release was attenuated; plasma aldosterone levels were reduced and adrenocorticotropic hormone-stimulated corticosteroid release was attenuated. In addition, V1a receptor expression was detected in macula densa cells of the kidneys, which may have facilitated renin production from the juxtaglomerular cells. Deletion of the V1a receptor appears to impact the renin-angiotensin-aldosterone system. Studies on V1a(-/-) mice revealed that non-vascular V1a receptors in the central nervous system and peripheral tissues play critical roles in the maintenance of blood pressure homeostasis.
当精氨酸血管加压素以足以激活血管 V1a 亚型血管加压素受体的量给药时，血压会迅速升高。然而，内源性血管加压素-V1a 系统是否有助于在正常发育和衰老过程中维持基础血压一直存在争议。缺乏 V1a 受体基因（V1a(-/-)）的突变小鼠与对照小鼠相比，血压明显降低，而心率没有明显变化。在 V1a(-/-)小鼠中，由于压力感受器反射中心功能障碍，动脉压力感受器反射减弱，并且小鼠的循环血量明显减少。与循环血量减少一致，肾上腺皮质激素释放减弱；血浆醛固酮水平降低，促肾上腺皮质激素刺激的皮质类固醇释放减弱。此外，V1a 受体在肾脏的致密斑细胞中表达，这可能有助于从肾小球旁细胞中产生肾素。V1a 受体的缺失似乎会影响肾素-血管紧张素-醛固酮系统。对 V1a(-/-) 小鼠的研究表明，中枢神经系统和外周组织中的非血管 V1a 受体在维持血压平衡方面发挥着关键作用。
