Objective: As a well-known traditional Chinese medicine formula prescribed by academician Ke-ji Chen, Qingda granule (QDG) lowered the blood pressure of spontaneously hypertensive rats and attenuated hypertensive cardiac remodeling and inflammation. However, its functional role and underlying mechanisms on hypertensive vascular function remain largely unclear. This study aims to assess the effects of QDG treatment on Angiotensin II- (AngII-) induced hypertension and vascular function and explore its underlying mechanisms both in vitro and in vivo.Methods: In an in vivo study, 25 male C57BL/6 mice were randomly divided into five groups, including Control, AngII, AngII + QDG-L, AngII + QDG-M, and AngII + QDG-H groups (n = 5 for each group). Mice in AngII and AngII + QDG-L/-M/-H groups were infused with AngII (500 ng/kg/min), while in the Control group, they were infused with saline. Mice in AngII + QDG were intragastrically given different concentrations of QDG (0.5725, 1.145, or 2.29 g/kg/day), while in Control and AngII groups, they were intragastrically given equal volumes of double distilled water for 2 weeks. Blood pressure was determined at 0, 1, and 2 weeks of treatment. Ultrasound was used to detect the pulse wave velocity (PWV) and HE staining to detect the pathological change of the abdominal aorta. RNA sequencing (RNA-seq) was performed to identify the differentially expressed transcripts (DETs) and related signaling pathways. IHC was used to detect the expression of p-ERK in the abdominal aorta. Primary isolated rat vascular smooth muscle cells (VSMCs) were used to assess the cellular Ca2+ release and activation of the ERK pathway by confocal microscope and western blotting analysis, respectively.Results: QDG treatment significantly alleviated the elevated blood pressure, the PWV, and the thickness of the abdominal aorta in AngII-induced hypertensive mice. RNA-seq and KEGG analyses identified 1,505 DETs and multiple enriched pathways (including vascular contraction and calcium signaling pathway) after QDG treatment. Furthermore, confocal microscope showed that QDG treatment partially attenuated the increase of Ca2+ release with the stimulation of AngII in cultured VSMCs. In addition, IHC and western blotting indicated that QDG treatment also partially alleviated the increase of phospho-ERK levels in abdominal aorta tissues of mice and cultured VSMCs after the infusion or stimulation of AngII.Conclusion: QDG treatment attenuated the elevation of blood pressure, abdominal aorta dysfunction, pathological changes, Ca2+ release, and activation of the ERK signaling pathway.

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Background: The association between isolated diastolic hypertension (IDH) and cardiovascular events has been inconsistently reported. This meta-analysis of cohort studies was designed to investigate the effect of the 2018 European Society of Cardiology (ESC) definition of IDH on the risk of composite cardiovascular events, cardiovascular mortality, all-cause mortality, and all strokes including ischemic stroke (IS) and hemorrhagic stroke (HS).Methods: PubMed, Embase, the Cochrane Library, and Web of Science were searched from inception to July 6, 2021. Cohort studies that investigated the association between IDH and cardiovascular events risk, compared to normotension, were included. Pooled hazard ratios (HRs) and 95% CIs were calculated using a random-effects models and heterogeneity was evaluated using Q-test and I2 statistic. The robustness of the associations was identified using sensitivity analysis. The methodological quality of the studies was assessed using the Newcastle–Ottawa scale. Publication bias was assessed using funnel plot, trim-and-fill method, Begg's test, and Egger's test.Results: A total of 15 cohort studies (13 articles) including 489,814 participants were included in this meta-analysis. The follow-up period ranged from 4.3 to 29 years. IDH was significantly associated with an increased risk of composite cardiovascular events (HR 1.28, 95% CI: 1.07–1.52, p = 0.006), cardiovascular mortality (HR 1.45, 95% CI: 1.07–1.95, p = 0.015), all strokes (HR 1.44, 95% CI: 1.04–2.01, p = 0.03), and HS (HR 1.64, 95% CI: 1.18–2.29, p = 0.164), but not associated with all-cause mortality (HR 1.20, 95% CI: 0.97–1.47, p = 0.087) and IS (HR 1.56, 95% CI: 0.87–2.81, p = 0.137). Subgroup analysis further indicated that IDH in the younger patients (mean age ≤ 55 years) and from Asia were significantly associated with an increased risk of composite cardiovascular events, while the elderly patients (mean age ≥ 55 years), Americans, and Europeans were not significantly associated with an increased risk of composite cardiovascular events.Conclusion: This meta-analysis provides evidence that IDH defined using the 2018 ESC criterion is significantly associated with an increased risk of composite cardiovascular events, cardiovascular mortality, all strokes and HS, but not significantly associated with all-cause death and IS. These findings also emphasize the importance for patients with IDH to have their blood pressure within normal, especially in the young adults and Asians.Trial Registration: PROSPERO, Identifier: CRD42021254108.