Altered contractile responses to angiotensin II and cholinergic stimulation in colonic circular smooth muscle from patients with diverticular disease.
6 affiliations
- 1Institute of Physiology and Pharmacology, Lithuanian University of Health Sciences, Kaunas, Lithuania.
- 2Department of Surgery, Lithuanian University of Health Sciences, Kaunas, Lithuania.
- 3Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas, Lithuania.
- 4Institute of Anatomy, Lithuanian University of Health Sciences, Kaunas, Lithuania.
- 5Department of Anesthesiology, Lithuanian University of Health Sciences, Kaunas, Lithuania.
- 6Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Abstract
Abnormal circular smooth muscle contractility is considered a key factor in the pathogenesis of diverticular disease (DD), contributing to increased intraluminal pressure and diverticulum formation. Altered cholinergic responsiveness of colonic smooth muscle has previously been reported in DD. Although angiotensin II (Ang II) regulates gastrointestinal smooth muscle contraction through angiotensin type 1 (AT1R) and type 2 (AT2R) receptors, its role in DD remains poorly understood. The aim of the present study was to investigate alterations in contractile responses to Ang II and cholinergic stimulation in the circular muscle of the colon in DD. Colonic tissue was obtained from 16 patients with DD and 16 control patients undergoing colorectal surgery. Immunofluorescence was performed to determine the localization of AT1R and AT2R. Ang II levels in colonic muscular tissue were quantified by enzyme-linked immunosorbent assay (ELISA), AT1R and AT2R protein expression were evaluated by Western blotting, and their mRNA expression was assessed by RT-qPCR. Circular smooth muscle strips were subsequently studied using in vitro organ bath recordings to assess Ang II-induced contractile responses under basal conditions and following pharmacological blockade with losartan, tetrodotoxin (TTX), or the AT2R antagonist PD123319. AT1R was predominantly localized in colonic smooth muscle cells, whereas AT2R was mainly detected in the myenteric plexus and nerve fibers. Compared with controls, DD tissues exhibited increased local Ang II levels and higher AT2R protein expression, accompanied by increased AT2R mRNA expression. Bethanechol-induced contractility was reduced in DD, whereas both peak and mean 5-min Ang II-induced contractile responses were enhanced. Losartan significantly reduced the mean 5-min Ang II-induced contractile response in both groups. However, both peak and mean responses remained significantly greater in DD than in controls following AT1R blockade. Neither TTX nor PD123319 significantly affected Ang II-induced contractions. The present study demonstrates altered colonic circular smooth muscle contractility in diverticular disease, characterized by enhanced responses to Ang II and reduced responses to cholinergic stimulation. The distinct muscular and neural distribution of AT1R and AT2R, respectively, suggests that altered local Ang II signaling, together with altered cholinergic regulation, may contribute to the pathogenesis of DD.
Related
- Inhibitory Effects of Gamma-Linolenic Acid on the Contractile Responses of Guinea Pig Ileal Longitudinal Smooth Muscle
- γ-Linolenic Acid Inhibits Contractile Responses in Pig Basilar Arteries via Prostanoid TP Receptor Antagonism and Ba²⁺-Sensitive K⁺ Channel Activation
- Anodal Transcranial Direct Current Stimulation Reduces Neuroinflammation and Cholinergic Dysregulation After Young Adult Traumatic Brain Injury
- Modeling the Relationship Between Stimulation Parameters and Motor Responses in PNS-TMS Paired Stimulation Using Gaussian Processes
- Transcutaneous auricular vagus nerve stimulation demonstrates effects on pupil responses in Parkinson's disease
BibTeX
@article{malinauskas2026altered,
title = {{Altered contractile responses to angiotensin II and cholinergic stimulation in colonic circular smooth muscle from patients with diverticular disease.}},
author = {Mantas Malinauskas and Justas Žilinskas and Darius Stukas and Kristina Rysevaite-Kyguoliene and Deividas Nekrosius and Henrikas Paužas and Andrius Macas and Anna Casselbrant},
journal = {Frontiers in physiology},
year = {2026},
month = oct,
doi = {10.3389/fphys.2026.1991333},
url = {https://europepmc.org/article/MED/42952718},
note = {CC BY},
}
RIS
TY - JOUR
TI - Altered contractile responses to angiotensin II and cholinergic stimulation in colonic circular smooth muscle from patients with diverticular disease.
AU - Mantas Malinauskas
AU - Justas Žilinskas
AU - Darius Stukas
AU - Kristina Rysevaite-Kyguoliene
AU - Deividas Nekrosius
AU - Henrikas Paužas
AU - Andrius Macas
AU - Anna Casselbrant
PY - 2026
DA - 2026/10/14
JO - Frontiers in physiology
DO - 10.3389/fphys.2026.1991333
UR - https://europepmc.org/article/MED/42952718
AB - Abnormal circular smooth muscle contractility is considered a key factor in the pathogenesis of diverticular disease (DD), contributing to increased intraluminal pressure and diverticulum formation. Altered cholinergic responsiveness of colonic smooth muscle has previously been reported in DD. Although angiotensin II (Ang II) regulates gastrointestinal smooth muscle contraction through angiotensin type 1 (AT1R) and type 2 (AT2R) receptors, its role in DD remains poorly understood. The aim of the present study was to investigate alterations in contractile responses to Ang II and cholinergic stimulation in the circular muscle of the colon in DD. Colonic tissue was obtained from 16 patients with DD and 16 control patients undergoing colorectal surgery. Immunofluorescence was performed to determine the localization of AT1R and AT2R. Ang II levels in colonic muscular tissue were quantified by enzyme-linked immunosorbent assay (ELISA), AT1R and AT2R protein expression were evaluated by Western blotting, and their mRNA expression was assessed by RT-qPCR. Circular smooth muscle strips were subsequently studied using in vitro organ bath recordings to assess Ang II-induced contractile responses under basal conditions and following pharmacological blockade with losartan, tetrodotoxin (TTX), or the AT2R antagonist PD123319. AT1R was predominantly localized in colonic smooth muscle cells, whereas AT2R was mainly detected in the myenteric plexus and nerve fibers. Compared with controls, DD tissues exhibited increased local Ang II levels and higher AT2R protein expression, accompanied by increased AT2R mRNA expression. Bethanechol-induced contractility was reduced in DD, whereas both peak and mean 5-min Ang II-induced contractile responses were enhanced. Losartan significantly reduced the mean 5-min Ang II-induced contractile response in both groups. However, both peak and mean responses remained significantly greater in DD than in controls following AT1R blockade. Neither TTX nor PD123319 significantly affected Ang II-induced contractions. The present study demonstrates altered colonic circular smooth muscle contractility in diverticular disease, characterized by enhanced responses to Ang II and reduced responses to cholinergic stimulation. The distinct muscular and neural distribution of AT1R and AT2R, respectively, suggests that altered local Ang II signaling, together with altered cholinergic regulation, may contribute to the pathogenesis of DD.
SN - 1664-042X
ER -