PMID- 38302836
OWN - NLM
STAT- Publisher
LR  - 20240201
IS  - 1573-4919 (Electronic)
IS  - 0300-8177 (Linking)
DP  - 2024 Feb 1
TI  - Inhibitors of gastric acid secretion increase oxidative stress and matrix 
      metalloproteinase-2 activity leading to vascular remodeling.
LID - 10.1007/s11010-023-04921-x [doi]
AB  - The use of inhibitors of gastric acid secretion (IGAS), especially proton pump 
      inhibitors (PPI), has been associated with increased cardiovascular risk. While 
      the mechanisms involved are not known, there is evidence supporting increased 
      oxidative stress, a major activator of matrix metalloproteinases (MMP), as an 
      important player in such effect. However, there is no study showing whether other 
      IGAS such as histamine H2-receptor blockers (H2RB) cause similar effects. This 
      study aimed at examining whether treatment with the H2RB ranitidine promotes 
      oxidative stress resulting in vascular MMP activation and corresponding 
      functional and structural alterations in the vasculature, as compared with those 
      found with the PPI omeprazole. Male Wistar rats were treated (4 weeks) with 
      vehicle (2% tween 20), omeprazole (10 mg/Kg/day; i.p.) or ranitidine (100 
      mg/Kg/day; gavage). Then the aorta was collected to perform functional, 
      biochemical, and morphometric analysis. Both ranitidine and omeprazole increased 
      gastric pH and oxidative stress assessed in situ with the fluorescent dye 
      dihydroethidium (DHE) and with lucigenin chemiluminescence assay. Both IGAS 
      augmented vascular activated MMP-2. These findings were associated with aortic 
      remodeling (increased media/lumen ratio and number of cells/mum(2)). Both IGAS 
      also impaired the endothelium-dependent relaxation induced by acetylcholine 
      (isolated aortic ring preparation). This study provides evidence that the H2RB 
      ranitidine induces vascular dysfunction, redox alterations, and remodeling 
      similar to those found with the PPI omeprazole. These findings strongly suggest 
      that IGAS increase oxidative stress and matrix metalloproteinase-2 activity 
      leading to vascular remodeling, which helps to explain the increased 
      cardiovascular risk associated with the use of those drugs.
CI  - (c) 2024. The Author(s), under exclusive licence to Springer Science+Business 
      Media, LLC, part of Springer Nature.
FAU - Nogueira, Renato C
AU  - Nogueira RC
AD  - Department of Pharmacology, Ribeirao Preto Medical School, University of Sao 
      Paulo, Av. Bandeirantes 3900, Ribeirao Preto, 14049-900, Brazil.
FAU - Sanches-Lopes, Jessica M
AU  - Sanches-Lopes JM
AD  - Department of Pharmacology, Ribeirao Preto Medical School, University of Sao 
      Paulo, Av. Bandeirantes 3900, Ribeirao Preto, 14049-900, Brazil.
FAU - Oliveira-Paula, Gustavo H
AU  - Oliveira-Paula GH
AD  - Department of Pharmacology, Ribeirao Preto Medical School, University of Sao 
      Paulo, Av. Bandeirantes 3900, Ribeirao Preto, 14049-900, Brazil.
AD  - Division of Cardiology, Department of Medicine, Wilf Family Cardiovascular 
      Research Institute, Albert Einstein College of Medicine, Bronx, NY, USA.
FAU - Tanus-Santos, Jose E
AU  - Tanus-Santos JE
AUID- ORCID: 0000-0002-9945-9633
AD  - Department of Pharmacology, Ribeirao Preto Medical School, University of Sao 
      Paulo, Av. Bandeirantes 3900, Ribeirao Preto, 14049-900, Brazil. 
      tanus@fmrp.usp.br.
LA  - eng
GR  - Finance Code 001/Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior/
GR  - Finance Code 001/Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior/
GR  - Finance Code 001/Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior/
GR  - 2014-23946-0/Fundacao de Aparo a Pesquisa do Estado de Sao Paulo/
GR  - 406442/2022-3/Conselho Nacional de Desenvolvimento Cientifico e Tecnologico/
PT  - Journal Article
DEP - 20240201
PL  - Netherlands
TA  - Mol Cell Biochem
JT  - Molecular and cellular biochemistry
JID - 0364456
SB  - IM
OTO - NOTNLM
OT  - MMP-2
OT  - Omeprazole
OT  - Oxidative stress
OT  - Ranitidine
OT  - Vascular remodeling
EDAT- 2024/02/02 00:42
MHDA- 2024/02/02 00:42
CRDT- 2024/02/01 23:58
PHST- 2023/10/31 00:00 [received]
PHST- 2023/12/20 00:00 [accepted]
PHST- 2024/02/02 00:42 [medline]
PHST- 2024/02/02 00:42 [pubmed]
PHST- 2024/02/01 23:58 [entrez]
AID - 10.1007/s11010-023-04921-x [pii]
AID - 10.1007/s11010-023-04921-x [doi]
PST - aheadofprint
SO  - Mol Cell Biochem. 2024 Feb 1. doi: 10.1007/s11010-023-04921-x.