Chronic hypertension increases aortic endothelial hydraulic conductivity by upregulating endothelial aquaporin-1 expression.

Numerous studies have examined the role of aquaporins in osmotic water transport in various systems, but virtually none have focused on the role of aquaporin in hydrostatically driven water transport involving mammalian cells save for our laboratory's recent study of aortic endothelial cells. Here, we investigated aquaporin-1 expression and function in the aortic endothelium in two high-renin rat models of hypertension, the spontaneously hypertensive genetically altered Wistar-Kyoto rat variant and Sprague-Dawley rats made hypertensive by two-kidney, one-clip Goldblatt surgery. We measured aquaporin-1 expression in aortic endothelial cells from whole rat aortas by quantitative immunohistochemistry and function by measuring the pressure-driven hydraulic conductivities of excised rat aortas with both intact and denuded endothelia on the same vessel. We used them to calculate the effective intimal hydraulic conductivity, which is a combination of endothelial and subendothelial components. We observed well-correlated enhancements in aquaporin-1 expression and function in both hypertensive rat models as well as in aortas from normotensive rats whose expression was upregulated by 2 h of forskolin treatment. Upregulated aquaporin-1 expression and function may be a response to hypertension that critically determines conduit artery vessel wall viability and long-term susceptibility to atherosclerosis.NEW & NOTEWORTHY The aortic endothelia of two high-renin hypertensive rat models express greater than two times the aquaporin-1 and, at low pressures, have greater than two times the endothelial hydraulic conductivity of normotensive rats. Data are consistent with theory predicting that higher endothelial aquaporin-1 expression raises the critical pressure for subendothelial intima compression and for artery wall hydraulic conductivity to drop.

Aquaporin-1 facilitates pressure-driven water flow across the aortic endothelium.

Aquaporin-1, a ubiquitous water channel membrane protein, is a major contributor to cell membrane osmotic water permeability. Arteries are the physiological system where hydrostatic dominates osmotic pressure differences. In the present study, we show that the walls of large conduit arteries constitute the first example where hydrostatic pressure drives aquaporin-1-mediated transcellular/transendothelial flow. We studied cultured aortic endothelial cell monolayers and excised whole aortas of male Sprague-Dawley rats with intact and inhibited aquaporin-1 activity and with normal and knocked down aquaporin-1 expression. We subjected these systems to transmural hydrostatic pressure differences at zero osmotic pressure differences. Impaired aquaporin-1 endothelia consistently showed reduced engineering flow metrics (transendothelial water flux and hydraulic conductivity). In vitro experiments with tracers that only cross the endothelium paracellularly showed that changes in junctional transport cannot explain these reductions. Percent reductions in whole aortic wall hydraulic conductivity with either chemical blocking or knockdown of aquaporin-1 differed at low and high transmural pressures. This observation highlights how aquaporin-1 expression likely directly influences aortic wall mechanics by changing the critical transmural pressure at which its sparse subendothelial intima compresses. Such compression increases transwall flow resistance. Our endothelial and historic erythrocyte membrane aquaporin density estimates were consistent. In conclusion, aquaporin-1 significantly contributes to hydrostatic pressure-driven water transport across aortic endothelial monolayers, both in culture and in whole rat aortas. This transport, and parallel junctional flow, can dilute solutes that entered the wall paracellularly or through endothelial monolayer disruptions. Lower atherogenic precursor solute concentrations may slow their intimal entrainment kinetics.

Zinc Supplementation Associated With a Decrease in Mortality in COVID-19 Patients: A Meta-Analysis.

The COVID-19 pandemic has had a significant impact on the world, resulting in millions of deaths worldwide and imposing economic, political, and social problems. The use of nutritional supplementation for the prevention and mitigation of COVID-19 remains controversial. This meta-analysis aims to investigate the association between zinc supplementation, mortality, and symptomatology, among COVID-19-infected patients. A meta-analysis was conducted to compare the outcomes of mortality and symptomology of patients with COVID-19 receiving zinc supplementation and those not receiving zinc supplementation. PubMed/Medline, Cochrane, Web of Science, and CINAHL Complete were independently searched with the search terms "zinc" AND "covid" OR "sars-cov-2" "COVID-19" OR "coronavirus". After duplicates were removed, 1215 articles were identified. Five of these studies were used to assess mortality outcomes, and two were used to assess symptomatology outcomes. The meta-analysis was conducted through R 4.2.1 software (R Foundation, Vienna, Austria). Heterogeneity was evaluated by calculating the I2 index. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used. It was found that COVID-19-infected individuals treated with zinc supplements had a reduced risk of mortality compared with individuals not treated with a zinc supplement RR=0.63 (95%CI;0.52,0.77), p=0.005. For symptomology, it was found that COVID-19-infected individuals treated with zinc had no difference in symptomology than individuals not treated with a zinc supplement RR=0.52 (95%CI;0.00,24315.42), p=0.578. This data indicates that zinc supplementation is associated with decreased mortality in those with COVID-19 but does not change symptomatology. This is promising as zinc is widely available and may be valuable as a cost-effective way to prevent poor outcomes for those with COVID-19.