Shouei Ishimaru, Satoshi Mizuno, Tomoya Tanada, Daisuke Saito, Keiichi Hirono, Keijiro Ibuki, Masato Taguchi
University of Toyama.
Japan
Yakugaku Zasshi (Journal of the Pharmaceutical Society of Japan)
Yakugaku Zasshi 2026;
DOI: 10.1248/yakushi.25-00165
Abstract
Pulmonary arterial hypertension (PAH) is a progressive pulmonary vascular disease that leads to right heart failure and systemic venous congestion. Such congestion can impair multiple organs, including the gastrointestinal tract. Recent clinical studies have reported elevated circulating endotoxin levels in patients with PAH, suggesting a potential disruption of intestinal barrier function. However, whether PAH affects duodenal permeability remains unclear. This study aimed to elucidate the impact of PAH on duodenal barrier integrity. PAH was induced in rats through two subcutaneous injections of monocrotaline (20 mg/kg). Histological analysis was performed, and the mRNA expression levels of duodenal tight junction proteins were quantified using real-time PCR. Duodenal permeability was assessed by performing in situ and ex vivo experiments with paracellular probes. PAH rats exhibited characteristic signs of right heart failure, including reduced weight gain, elevated brain natriuretic peptide levels, and thickening of the right ventricular wall. Histological examination revealed duodenal villous atrophy and thickened muscularis mucosa. Claudin-1 mRNA expression in the duodenum of PAH rats was 70% lower than that in control rats. In situ permeability assays revealed 2.0- and 1.5-fold increases in the portal vein concentrations of polyethylene glycol 400 and 600, respectively. In addition, ex vivo experiments showed a 1.9-fold increase in the cumulative lactulose permeation from the luminal to the vascular side over 120 min. To the best of our knowledge, this is the first report to describe decreased duodenal barrier integrity caused by monocrotaline-induced PAH in rats.
Category
Class I. Drug-induced and Toxin-induced Pulmonary Hypertension
Animal Models of Pulmonary Vascular Disease and Therapy
Acquired Patient Factors Associated with Pulmonary Vascular Disease
Age Focus: No Age-Related Focus
Fresh or Filed Publication: Fresh (PHresh). Less than 1-2 years since publication
Article Access
Free PDF File or Full Text Article Available Through PubMed or DOI: Yes (Japanese)