Selective deletion of endothelial mineralocorticoid receptor protects from vascular dysfunction in sodium-restricted female mice.

BACKGROUND: Recent evidence by our laboratory demonstrates that women and female mice endogenously express higher endothelial mineralocorticoid receptor (ECMR) than males. Mounting clinical evidence also indicates that aldosterone production is higher in pathological conditions in females compared to males. However, the role for increased activation of ECMR by aldosterone in the absence of a comorbid condition is yet to be explored. The current study hypothesized that increased ECMR activation induced by elevated aldosterone production predisposes healthy female mice to endothelial dysfunction. METHOD: Vascular reactivity was assessed in aortic rings from wild-type (WT) and ECMR KO (KO) mice fed either a normal salt (NSD, 0.4% NaCl) or sodium-restricted diet (SRD, 0.05% NaCl) for 28 days. RESULTS: SRD elevated plasma aldosterone levels as well as adrenal CYP11B2 and angiotensin II type 1 receptor (AT1R) expressions in female, but not male, WT mice. In baseline conditions (NSD), endothelial function, assessed by vascular relaxation to acetylcholine, was higher while vascular contractility to phenylephrine, serotonin, and KCl lower in female than male WT mice. SRD impaired endothelial function and increased vascular contractility in female, but not male, WT mice effectively ablating the baseline sex differences. NOS inhibition with LNAME ablated endothelial relaxation to a higher extent in male than female mice on NSD and ablated differences in acetylcholine relaxation responses between NSD- and SRD-fed females, indicating a role for NO in SRD-mediated endothelial function. In association, SRD significantly reduced vascular NOX4 expression in female, but not male, mice. Lastly, selective deletion of ECMR protected female mice from SRD-mediated endothelial dysfunction and increased vascular contractility. CONCLUSION: Collectively, these data indicate that female mice develop aldosterone-induced endothelial dysfunction via endothelial MR-mediated reductions in NO bioavailability. In addition, these data support a role for ECMR to promote vascular contractility in female mice in response to sodium restriction.

Rates of hepatitis B and C in patients with schizophrenia: A meta-analysis.

OBJECTIVE: Schizophrenia is associated with increased infectious disease comorbidity and mortality. Individuals with schizophrenia have increased risk of infectious hepatitis, potentially due to substance use comorbidity, sexual behaviors, and immunologic factors. We performed a systematic review and meta-analysis of the association between schizophrenia and hepatitis B and C. METHOD: We searched major electronic databases from inception until January 2019 for prevalence and case-control studies of infectious hepatitis in patients with schizophrenia. Random effects meta-analyses calculating odds ratios (ORs) and 95% confidence intervals (CIs) for case-controls studies, prevalence and 95% CIs, and meta-regression analyses were performed. RESULTS: Twenty-one studies met the inclusion criteria. In case-control studies, there was an over 3-fold increased odds of hepatitis C in patients with schizophrenia (OR = 3.29, 95% CI 1.50-7.23, p = 0.003), and a prevalence of 6% (ES = 0.06, 95% CI 0.04-0.08). In case-control studies, there was an over 2-fold increased odds of hepatitis B in patients with schizophrenia (OR = 2.36, 95% CI 1.61-3.47, p < 0.001) and a prevalence of 7% (ES = 0.07, 95% CI 0.03-0.11). CONCLUSION: We found an approximately 3-fold increased odds of hepatitis B and C in patients with schizophrenia. This association may be due to an increased prevalence of environmental risk factors, increased susceptibility to infections, or both. Findings suggest that screening for infectious hepatitis may be germane to the clinical care of patients with schizophrenia and relevant risk factors.