高血压病是严重危害人类健康疾病，肾素-血管紧张素系统(RAS)在其中起重要作用。研究提示作为G蛋白偶联受体的钙敏感受体(CaSR)可能有调节血压作用，机制不明。而肾小球球旁细胞CaSR激活经细胞内钙离子浓度（[Ca2+]i）增加，可抑制腺苷酸环化酶(AC)，减少cAMP形成和肾素释放。预实验发现：CaSR激活可降低自发性高血压大鼠(SHR)血压，SHR血管平滑肌细胞CaSR表达降低且对CaSR激动剂反应减弱。我们推测：在SHR体内，由于CaSR表达下降或功能缺陷使[Ca2+]i降低，对AC抑制作用减弱，使cAMP和肾素增加，激活RAS介导了血管收缩及平滑肌增殖重塑，促进了高血压发生。为证实此假说，本项目拟在整体、组织和细胞分子三个层面研究CaSR与高血压相关性及在SHR降血压、调节血管张力等方面作用及与AC和RAS活性变化关系，阐明CaSR在高血压发病中作用和机制，为高血压防治提供新标靶。

Essential hypertension (EH) is a serious disease which is harmful to human health, and the renin-angiotensin system (RAS) plays an important role in the pathogenesis processes of EH. The extracellular calcium-sensing receptor (CaSR) is a G protein-coupled receptors and the data suggest that CaSR may have a role in regulating blood pressure. However, the underlying pathologic mechanisms are poorly understood.The investigations demonstrated that stimulating CaSR of renal juxtaglomerular (JG) cells could activate G(q) leading to the generation of inositol 1,4,5-trisphophate (IP3),and the release of Ca2+ from the endoplasmic reticulum (ER),increasing intracellular calcium concentration ([Ca2+]i), and resulting in calcium-mediated renin inhibition by inhibition of adenylate cyclase V (adenylyl cyclase isoform V, AC-V) and to reduce the cyclic adenosine monophosphate (cAMP) formation. Our preliminary experiment results show that CaSR activation can reduce spontaneous hypertensive rats (SHR) blood pressure; CaSR expression and the response to CaSR agonist were decreased in SHR vascular smooth muscle cells (VSMC). Therefore, we hypothesized that in SHR, because of CaSR expression and/or function impairment resulted in [Ca2+]i decrease by PLC/IP3 pathway, weakening of AC-V inhibition and increased cAMP formation and renin release. RAS activation proceeds and evokes vasoconstriction,vascular smooth muscle proliferation and remodeling, promoting the development of hypertension. To prove this hypothesis, based on vivo, tissue ,cell and molecular levels, we intend to study the relationship between CaSR and hypertension, its roles in decrease SHR blood pressure,regulation angiotasis and vascular smooth muscle proliferation and remodeling as well as cAMP contents and RAS activity change. Eventually, we clarify the effects of CaSR on hypertension and its mechanisms and to provide a new clinical target for the prevention and treatment of hypertension.