title: Reduced Expression of the Extracellular Calcium-Sensing Receptor (CaSR) Is Associated with Activation of the Renin-Angiotensin System (RAS) to Promote Vascular Remodeling in the Pathogenesis of Essential Hypertension.
abstract: The proliferation of vascular smooth muscle cells (VSMCs), remodeling of the vasculature, and the renin-angiotensin system (RAS) play important roles in the development of essential hypertension (EH), which is defined as high blood pressure (BP) in which secondary causes, such as renovascular disease, are absent. The calcium-sensing receptor (CaSR) is involved in the regulation of BP. However, the underlying mechanisms by which the CaSR regulates BP are poorly understood. In the present study, the role of the CaSR in EH was investigated using male spontaneously hypertensive rats (SHRs) and rat and human plasma samples. The percentages of medial wall thickness to external diameter (WT%), total vessel wall cross-sectional area to the total area (WA%) of thoracic arteries, as well as the percentage of wall area occupied by collagen to total vessel wall area (CA%) were determined. Tissue protein expression and plasma concentrations of the CaSR, cyclic adenosine monophosphate (cAMP), renin, and angiotensin II (Ang II) were additionally assessed. WT%, WA%, and CA% were found to increase with increasing BP, whereas the plasma concentration of CaSR was found to decrease. With increasing BP, the levels of smooth muscle actin and calponin decreased, whereas those of osteopontin and proliferating cell nuclear antigen increased. The CaSR level negatively correlated with the levels of cAMP and Ang II, but positively correlated with those of renin. Our data suggest that reduced expression of the CaSR is correlated with activation of the RAS, which induces increased vascular remodeling and VSMC proliferation, and thereby associated with EH in the SHR model and in the Han Chinese population. Our findings provide new insights into the pathogenesis of EH.
authors.affiliation: Department of Pathophysiology/Key Laboratory of Education Ministry of Xinjiang Endemic and Ethnic Diseases, Medical College of Shihezi University, Shihezi, China.|Department of Emergency and critical care medicine, the First Affiliated Hospital of Medical College of Shihezi University, Shihezi, 832008, China.
authors.forename: Yuan-Yuan
authors.initials: YY
authors.lastname: Qu
authors.affiliation: Department of Pathophysiology/Key Laboratory of Education Ministry of Xinjiang Endemic and Ethnic Diseases, Medical College of Shihezi University, Shihezi, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Hui
authors.affiliation: Centre of Medical Functional Experiments, Medical College of Shihezi University, Shihezi, China.
authors.forename: La-Mei
authors.initials: LM
authors.lastname: Wang
authors.affiliation: Department of Pathophysiology/Key Laboratory of Education Ministry of Xinjiang Endemic and Ethnic Diseases, Medical College of Shihezi University, Shihezi, China.
authors.forename: Na
authors.initials: N
authors.lastname: Tang
authors.affiliation: Department of Pathophysiology/Key Laboratory of Education Ministry of Xinjiang Endemic and Ethnic Diseases, Medical College of Shihezi University, Shihezi, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Zhong
authors.affiliation: Department of Pathophysiology/Key Laboratory of Education Ministry of Xinjiang Endemic and Ethnic Diseases, Medical College of Shihezi University, Shihezi, China.
authors.forename: Yong-Min
authors.initials: YM
authors.lastname: Liu
authors.affiliation: Department of Pathophysiology/Key Laboratory of Education Ministry of Xinjiang Endemic and Ethnic Diseases, Medical College of Shihezi University, Shihezi, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Pathophysiology/Key Laboratory of Education Ministry of Xinjiang Endemic and Ethnic Diseases, Medical College of Shihezi University, Shihezi, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Feng
authors.affiliation: Department of Pathophysiology/Key Laboratory of Education Ministry of Xinjiang Endemic and Ethnic Diseases, Medical College of Shihezi University, Shihezi, China.
authors.forename: Fang
authors.initials: F
authors.lastname: He
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure; D049109:Cell Proliferation; D002681:China; D000075222:Essential Hypertension; D005260:Female; D006801:Humans; D006973:Hypertension / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D051381:Rats; D011918:Rats, Inbred SHR; D044169:Receptors, Calcium-Sensing / Q000378:metabolism*; D012084:Renin-Angiotensin System; D066253:Vascular Remodeling / Q000502:physiology; D055815:Young Adult
chemical_list: C095550:CASR protein, human; D044169:Receptors, Calcium-Sensing; C473605:extracellular calcium cation-sensing receptor, rat; D000804:Angiotensin II