Background Controversy exists regarding the drug selection in hypertension (HTN) management in patients with COVID‐19. This study aimed to compare the effects of losartan and amlodipine in patients with primary HTN and COVID‐19. Methods In this randomised clinical trial, hospitalised patients with COVID‐19 and primary HTN were enrolled in the study. One arm received losartan, 25 mg, twice a day and the other arm received amlodipine, 5 mg per day for 2 weeks. The main outcomes were compare 30‐day mortality rate and length of hospital stay. Results The mean age of patients treated with losartan (N = 41) and amlodipine (N = 39) was 67.3 ± 14.8 and 60.1 ± 17.3 years, respectively (P value = .068). The length of hospital stay in losartan and amlodipine groups was 4.57 ± 2.59 and 7.30 ± 8.70 days, respectively (P value = .085). Also, the length of ICU admission in losartan and amlodipine group was 7.13 ± 5.99 and 7.15 ± 9.95 days, respectively (P value = .994). The 30‐day mortality was two and five patients in losartan and amlodipine groups, respectively (P value = .241). Conclusions There was no priority in losartan or amlodipine administration in COVID‐19 patients with primary HTN in decreasing mortality rate, hospital and ICU length stay. Further studies need to clarify the first‐line anti‐HTN medications in COVID‐19.
Background. The risk factors for acute kidney injury (AKI) development in patients with diabetes hospitalized for COVID-19 have not been fully studied yet. In this study, we aimed to estimate the rate of AKI among the hospitalized population with COVID-19 and to identify the risk factors associated with AKI among patients with diabetes. Material and Methods. This retrospective cohort study included 254 patients (127 with diabetes and 127 without diabetes) who were admitted for COVID-19 to a tertiary hospital in Tehran, Iran, between February and May 2020. Clinical characteristics and outcomes, radiological findings, and laboratory data, including data on AKI, hematuria, and proteinuria were recorded and analyzed. Results. Of 254 patients, 142 (55.9%) were male and the mean (± SD) age was 65.7 years (±12.5). In total, 58 patients (22.8%) developed AKI during hospitalization, of whom 36 patients had diabetes ( p = 0.04 ); most patients (74.1%) had stage 1 or 2 AKI. Also, 8 patients (13.8%) required renal replacement therapy (RRT) after developing AKI. Regardless of diabetes status, patients who developed AKI had significantly higher mortality rates compared with patients who did not develop AKI ( p = 0.02 ). Hematuria and proteinuria were observed in 38.1% and 55% of patients, respectively. Multivariate analysis showed that invasive mechanical ventilation, proteinuria, HBA1c level, history of cardiovascular disease, and use of statins were independent risk factors for AKI development in patients with diabetes. Conclusion. Results of this study showed that AKI develops in a considerable percentage of patients with COVID-19, especially in those with diabetes, and is significantly associated with mortality.
Concentric pulmonary vascular wall thickening due partially to increased PASMC proliferation contributes to elevating PVR in patients with pulmonary hypertension (PH). While pulmonary vasoconstriction may be an early contributor to increasing PVR, the transition of contractile PASMCs to proliferative PASMCs may play an important role in the development and progression of pulmonary vascular remodeling in PH. A rise in cytosolic Ca2+ concentration ([Ca2+]cyt) is a trigger for PASMC contraction and proliferation. Here we report that upregulation of Piezo1, a mechanosensitive cation channel, is involved in the contractile-to-proliferative phenotypic transition of PASMCs and development of pulmonary vascular remodeling. By comparing freshly isolated PA (contractile PASMCs) and primary cultured PASMCs in growth medium (proliferative PASMCs), we found that Piezo1, Notch2/3 and CaSR protein levels were significantly higher in proliferative PASMCs than in contractile PASMCs. Upregulated Piezo1 was associated with an increase in expression of PCNA, a marker for cell proliferation, whereas downregulation (with siRNA) or inhibition (with GxMTx4) of Piezo1 attenuated PASMC proliferation. Furthermore, Piezo1 in the remodeled PA from rats with experimental PH was upregulated in comparison to PA from control rats. These data indicate that PASMC contractile-to-proliferative phenotypic transition is associated with the transition or adaptation of membrane channels and receptors. Upregulated Piezo1 may play a critical role in PASMC phenotypic transition and PASMC proliferation. Upregulation of Piezo1 in proliferative PASMCs may likely be required to provide sufficient Ca2+ to assure nuclear/cell division and PASMC proliferation, contributing to the development and progression of pulmonary vascular remodeling in PH.
Mechanosensitive cation channels and Ca2+ influx through these channels play an important role in regulating endothelial cell functions. TRPC6 is a diacylglycerol-sensitive non-selective cation channel that forms receptor-operated Ca2+ channels in a variety of cell types. Piezo1 is a mechanosensitive cation channel activated by membrane stretch and shear stress in lung endothelial cells. In this study, we report that TRPC6 and Piezo1 channels both contribute to membrane stretch-mediated cation currents and Ca2+ influx or increase in cytosolic free Ca2+ concentration ([Ca2+]cyt) in human pulmonary arterial endothelial cells (PAECs). The membrane stretch-mediated cation currents and increase in [Ca2+]cyt in human PAECs were significantly decreased by GsMTX4, a blocker of Piezo1 channels and by BI-749327, a selective blocker of TRPC6 channels. Extracellular application of OAG, a membrane permeable analogue of diacylglycerol, rapidly induced whole-cell cation currents and increased [Ca2+]cyt in human PAECs and HEK-cells transiently transfected with the human TRPC6 gene. Furthermore, membrane stretch with hypoosmotic or hypotonic solution enhances the cation currents in TRPC6-transfected HEK cells. In HEK cells transfected with the Piezo1 gene, however, OAG had little effect on the cation currents, but membrane stretch significantly enhanced the cation currents. These data indicate that, while both TRPC6 and Piezo1 are involved in generating mechanosensitive cation currents and increases in [Ca2+]cyt in human PAECs undergoing mechanical stimulation, only TRPC6 (but not Piezo1) is sensitive to the second messenger diacylglycerol. Selective blockers of these channels may help develop novel therapies for mechanotransduction-associated pulmonary vascular remodeling in patients with pulmonary arterial hypertension.
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