Luteolin reduces high glucose-mediated impairment of endothelium-dependent relaxation in rat aorta by reducing oxidative stress

While luteolin, a flavone rich in many plants, has some cardiovascular activity, it is not clear whether luteolin has beneficial effects on the vascular endothelial impairment in hyperglycemia/high glucose. Here, we reveal the protective effect of luteolin on endothelium-dependent relaxation in isolated rat aortic rings exposed to high glucose. The thoracic aorta of male Sprague–Dawley rats was rapidly dissected out and the effect of luteolin on the tension of aortic rings pretreated with high glucose (44 mM) for 4 h was measured in an organ bath system. The levels of nitric oxide (NO), hydroxy radical (OH^?) and reactive oxygen species (ROS), and the activity of superoxide dismutase (SOD) and nitric oxide synthase (NOS) were measured in aortas. The vasorelaxation after treatment with luteolin for 8 weeks in aortic rings from diabetic rats was also determined. We found that exposure to high glucose decreased acetylcholine-induced endothelium-dependent relaxation. However, high mannitol had no effect on vasorelaxation. Luteolin evoked a concentration-dependent relaxation in aortic rings previously contracted by phenylephrine, and the pD₂ value was 5.24 ± 0.04. The EC₅₀ of luteolin markedly attenuated the inhibition of relaxation induced by high glucose, which was significantly weakened by pretreatment with l-NAME (0.1 mM), but not by indomethacin (0.01 mM). Luteolin significantly inhibited the increase of ROS level and OH^? formation, and the decrease of NO level, NOS and SOD activity caused by high glucose. The improving effect of luteolin on endothelium-dependent vasorelaxation in diabetic rat aortic rings was reversed by pretreatment with l-NAME or methylene blue. The results indicate that the decrease of endothelium-dependent relaxation in rat aortic rings exposed to high glucose is markedly attenuated by luteolin, which may be mediated by reducing oxidative stress and enhancing activity in the NOS–NO pathway.     

Looking for opportunities to co-enroll: The DISCOVERY study experience

BackgroundConducting high-quality stroke trials is complex and costly. Often these trials compete for the attention of researchers and the availability of patients. Enrolling patients in more than one study concurrently has the potential to accelerate recruitment into individual studies. DISCOVERY is a multicenter, inception cohort study of cognitive impairment and dementia following ischemic or hemorrhagic stroke. At the request of site investigators, a DISCOVERY committee reviews individual studies for approval of possible concurrent co-enrollment into DISCOVERY. The purpose of this report is to summarize the characteristics and outcomes of studies reviewed by committee for possible co-enrollment.MethodsThis analysis covers studies reviewed from 07/01/2020 to 04/26/2022 by the Site Management Committee (SMC) of the DISCOVERY Recruitment and Retention Core. Characterization of each study included study type, number and length of follow-up visits, and whether there were protocol-required blood draws, brain imaging studies, or cognitive tests. Studies were scored for patient burden and scientific overlap with Discovery. The primary outcome was SMC approval to co-enroll.Results59 studies were reviewed, and 69.5% (n = 41, 21 clinical trials; 20 observational studies) were found by the SMC to be appropriate for co-enrollment. Higher patient burden and greater scientific overlap with DISCOVERY reduced the rates of approval for co-enrollment.ConclusionA large number of diverse stroke studies are being run concurrently across the DISCOVERY study network, however, about two-thirds of the studies were considered appropriate for consideration of co-enrollment. Future studies should study how co-enrollment might improve trial network efficiency.