钙敏感受体降低血压并改善高血压视网膜血管改变 postprint

Abstract: Background Although clinical and basic experiments have paid attention to the role and mechanism of calcium-sensing receptors in hypertensive diseases, there is still a lack of relevant research on its role and mechanism in hypertensive retinal diseases. Objective To investigate the expression levels of calcium-sensitive receptors (CaSR) in the hypertensive retina and the relationship with myocardial remodeling and retinal vascular changes in hypertension. Methods Fifteen 8-week-old homologous healthy normotensive rats (WKY) were selected as the normotensive (WKY) group, and 30 same-week-old spontaneously hypertensive rats (SHR) were randomly divided into the hypertensive (SHR) group and the inhibitor (SHR+NPS2143) group. the SHR+NPS2143 group was injected intraperitoneally with the CaSR inhibitor NPS2143. Blood pressure were monitored by non-invasive blood pressure monitor. Retinal pathological changes were detected by hematoxylin and eosin staining (HE). Myocardial collagen deposition was observed by Masson staining. The distribution and expression of CaSR and vascular endothelial growth factor A (VEGFA) in the retina were observed by immunohistochemical staining and quantitative real-time fluorescence PCR (qRT-PCR). Results Compared with 8W and 24W WKY, the SHR group at the same week of age had increased blood pressure (P < 0.05), retinal structural disorder, increased thickness (P < 0.01), and reduced levels of CaSR expression and increased levels of VEGFA expression in the retina (P < 0.01), NPS2143 intervention up to 24W significantly increased SHR blood pressure (P < 0.05), retinal structural disorder aggravated with a significant increase in thickness (P < 0.01), and a further decrease in CaSR expression and a further increase in VEGFA expression in the retina (P < 0.01). Compared with the same week-old WKY, there was no statistical difference in HW/BW% and LVW/BW% in the 8W SHR group, and no significant increase in myocardial collagen accumulation was seen (P > 0.05), while HW/BW% and LVW/BW% were elevated and myocardial collagen accumulation was increased in the 24W SHR group, and NPS2143 intervention up to 24W significantly elevated HW/BW% and LVW/BW% in SHR. significantly increased the area of myocardial collagen accumulation in SHR (P < 0.05). Conclusion CaSR lowers blood pressure, improves myocardial remodeling, and delays the development of hypertension-induced retinal vasculopathy by inhibiting VEGFA expression.