Zhongguo quanke yixue (Feb 2023)
Role of Calcium-sensing Receptors in Myocardial Remodeling and Retinal Vasculopathy in Rat Models of Hypertension
Abstract
Background Clinical treatment of target organ damage in hypertension is mainly based on systemic hypotension supplemented by topical medication, but the treatment is unsatisfactory due to different or even mutually exclusive responses of tissues to the drugs. The relationship between calcium-sensing receptors (CaSR) and hypertension has been investigated, however, studies on their role and mechanisms in hypertensive retinal disease are still lacking. Objective To investigate the expression level of CaSR in hypertensive retina and its relationship with myocardial remodeling and retinal vascular changes in hypertension. Methods Ten 8-week-old healthy wistar-kyoto rats (WKY) were selected as the WKY group, and 20 homologous spontaneous hypertensive rats (SHR) of the same age were randomly divided into SHR group and inhibitor (SHR+NPS2143) group from May to December 2021. During a 16-week intervention, the SHR+NPS2143 group received intraperitoneal injection of CaSR inhibitor NPS2143, while WKY and SHR groups were intraperitoneally injected with the equal volume of normal saline. At baseline and the end of intervention, blood pressure was measured by non-invasive blood pressure monitor in all rats, and from each group, five rats were selected and executed, and myocardial and retinal tissues were taken out for testing. Masson's Trichrome staining was used to measure the collagen deposition in the myocardium. H & E staining was used to detect the pathological changes in retinal tissues. The distribution and expression of CaSR and vascular endothelial growth factor A (VEGFA) in retinal tissues were detected using immunohistochemical staining and qRT-PCR. Results SHR group had significantly higher levels of systolic blood pressure (SBP) , diastolic blood pressure (DBP) and mean arterial pressure (MAP) than WKY group either at baseline or the end of intervention (P<0.05) . SHR group had much lower levels of SBP, DBP and MAP levels than SHR+NPS2143 group at the end of intervention (P<0.05) . At the end of the intervention, a significant growth was found in SBP, DBP and MAP levels in both SHR and SHR+NPS2143 groups (P<0.05) . Compared with SHR group, heart weight/body weight ratio (HW/BW%) , left ventricle weight/body weight ratio (LVW/BW%) , and myocardial collagen volume fraction (CVF) were significantly decreased in WKY group but increased significantly in SHR+NPS2143 group (P<0.05) . A significant growth was found in HW/BW%, LVW/BW% and CVF in both SHR and SHR+NPS2143 groups (P<0.05) . The total retinal thickness and inner plexiform layer thickness were higher in SHR group than in WKY group at baseline and 16 weeks of intervention (P<0.05) . The total retinal thickness and inner plexiform layer thickness were lower in the SHR group than in the SHR+NPS2143 group at 16 weeks of intervention (P<0.05) . Compared with SHR group, the inner plexiform layer thickness at 16 weeks of intervention was decreased in WKY group and increased in SHR+NPS2143 group (P<0.05) . CaSR in the retina of SHR group was lower than that of WKY group but higher than that of SHR+NPS2143 group (P<0.05) at 16 weeks of intervention. VEGFA in the retina of SHR group was higher than that of WKY group but lower than that of SHR+NPS2143 group (P<0.05) at 16 weeks of intervention. Conclusion The use of CaSR inhibitor could reduce the activation of CaSR, increase the expression of VEGFA in the retina, exacerbate hypertension-induced myocardial remodeling and the development of retinal vasculopathy.
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