Effects of Beraprost on Intestinal Microcirculation and Barrier Function in a Mouse Model of Renal Failure

• Published in: Microcirculation (New York, N.Y. 1994) N.Y. 1994), 2024-11, Vol.31 (8), p.e12889-n/a
• Main Authors: Hirano, Akira, Kadoya, Hiroyuki, Takasu, Masanobu, Iwakura, Tsukasa, Kajimoto, Eriko, Tatsugawa, Rie, Matsuura, Takumi, Kurumatani, Hajimu, Yamamoto, Toshiya, Kidokoro, Kengo, Kishi, Seiji, Nagasu, Hajime, Sasaki, Tamaki, Kashihara, Naoki
• Format: Article
• Language: English
• Subjects: Animals; beraprost; Disease Models, Animal; endothelial dysfunction; Epoprostenol - analogs & derivatives; Epoprostenol - pharmacology; glycocalyx; Intestinal Mucosa - blood supply; Intestinal Mucosa - drug effects; Intestinal Mucosa - metabolism; Intestines - blood supply; Intestines - drug effects; Kidney diseases; Male; Mice; Mice, Inbred ICR; Microcirculation - drug effects; nitric oxide; Reactive oxygen species; Renal Insufficiency - drug therapy; Renal Insufficiency - physiopathology; tight junction
• ISSN: 1073-9688; 1549-8719; 1549-8719
• DOI: 10.1111/micc.12889

ABSTRACT Objective Endothelial dysfunction plays an important role in the pathogenesis of chronic kidney disease. Prostacyclin (PGI2), an endothelial cell‐produced endogenous prostaglandin, plays a crucial role in maintaining endothelial function. However, its effects on intestinal microcirculation and barrier function are not fully understood. We hypothesized that PGI2 improves intestinal microcirculation and barrier function via endothelial protective effects. Methods ICR and ICGN (a spontaneous nephrotic model) mice were used in this study. Intestinal microcirculation was visualized in vivo to investigate PGI2 effects. Beraprost served as PGI2. PGI2 administration spanned 4 weeks, following which we assessed its influence on intestinal endothelial, intestinal barrier, and renal functions. Results We visualized intestinal microcirculation and endothelial glycocalyx in the intestinal blood vessels. Beraprost administration induced a 1.2‐fold dilatation of the vascular diameter of the small intestine. Intestinal blood flow in ICGN mice was significantly reduced compared that in ICR mice but improved with beraprost administration. ICGN mice exhibited reduced serum albumin levels, decreased ambulation, an imbalance in intestinal reactive oxygen species (ROS)/nitric oxide (NO), and impaired tight junctions; all were ameliorated by beraprost administration. Conclusions Beraprost improves intestinal microcirculation and barrier function by ameliorating ROS/NO imbalances, thereby reducing physical inactivity during renal failure.