Angiotensin II AT1 receptor blockade decreases brain artery inflammation in a stress-prone rat strain
- PMID: 15240389
- DOI: 10.1196/annals.1296.043
Angiotensin II AT1 receptor blockade decreases brain artery inflammation in a stress-prone rat strain
Abstract
The spontaneously hypertensive rats (SHR) are a genetically hypertensive strain with vulnerability to brain ischemia and stress. In SHR, the brain Angiotensin II (Ang II) system is chronically stimulated, resulting in brain artery remodeling and inflammation. Pretreatment with Ang II AT(1) receptor antagonists protects from brain ischemia and prevents the hormonal and sympathoadrenal response to stress. In addition, the anti-inflammatory effects of AT(1) receptor antagonists are partially responsible for preventing the development of stress-induced gastric ulcers. We asked whether AT(1) receptor antagonists could exert anti-inflammatory effects in the brain vasculature as a mechanism for their protective effects against ischemia. As determined by immunohistochemistry, long-term inhibition of brain AT(1) receptors by peripheral administration of the AT(1) receptor antagonist candesartan (0.3 mg/kg/day for 28 days) normalized the pathologic remodeling, decreased expression of the intercellular adhesion molecule-1 and the number of associated macrophages, and normalized the endothelial nitric oxide synthase expression in cerebral vessels of SHR. The anti-inflammatory effects of AT(1) receptor antagonists may be an important mechanism for protection against ischemia and could participate in the anti-stress properties of this class of compounds.
Similar articles
-
Angiotensin II AT1 receptor blockade reverses pathological hypertrophy and inflammation in brain microvessels of spontaneously hypertensive rats.Stroke. 2004 Jul;35(7):1726-31. doi: 10.1161/01.STR.0000129788.26346.18. Epub 2004 May 13. Stroke. 2004. PMID: 15143297
-
Normalization of endothelial and inducible nitric oxide synthase expression in brain microvessels of spontaneously hypertensive rats by angiotensin II AT1 receptor inhibition.J Cereb Blood Flow Metab. 2003 Mar;23(3):371-80. doi: 10.1097/01.WCB.0000047369.05600.03. J Cereb Blood Flow Metab. 2003. PMID: 12621312
-
Anti-inflammatory effects of angiotensin II AT1 receptor antagonism prevent stress-induced gastric injury.Am J Physiol Gastrointest Liver Physiol. 2003 Aug;285(2):G414-23. doi: 10.1152/ajpgi.00058.2003. Epub 2003 Apr 9. Am J Physiol Gastrointest Liver Physiol. 2003. PMID: 12686508
-
Involvement of angiotensin II in cardiovascular and renal injury: effects of an AT1-receptor antagonist on gene expression and the cellular phenotype.J Hypertens Suppl. 1997 Dec;15(6):S3-7. J Hypertens Suppl. 1997. PMID: 9493120 Review.
-
Brain angiotensin II: new developments, unanswered questions and therapeutic opportunities.Cell Mol Neurobiol. 2005 Jun;25(3-4):485-512. doi: 10.1007/s10571-005-4011-5. Cell Mol Neurobiol. 2005. PMID: 16075377 Review.
Cited by
-
Amphetamine Induces Oxidative Stress, Glial Activation and Transient Angiogenesis in Prefrontal Cortex via AT1-R.Front Pharmacol. 2021 May 3;12:647747. doi: 10.3389/fphar.2021.647747. eCollection 2021. Front Pharmacol. 2021. PMID: 34012397 Free PMC article.
-
Candesartan, an angiotensin II AT₁-receptor blocker and PPAR-γ agonist, reduces lesion volume and improves motor and memory function after traumatic brain injury in mice.Neuropsychopharmacology. 2012 Dec;37(13):2817-29. doi: 10.1038/npp.2012.152. Epub 2012 Aug 15. Neuropsychopharmacology. 2012. PMID: 22892395 Free PMC article.
-
Long-term angiotensin II AT1 receptor inhibition produces adipose tissue hypotrophy accompanied by increased expression of adiponectin and PPARgamma.Eur J Pharmacol. 2006 Dec 15;552(1-3):112-22. doi: 10.1016/j.ejphar.2006.08.062. Epub 2006 Sep 9. Eur J Pharmacol. 2006. PMID: 17064684 Free PMC article.
-
Elevated blood pressure aggravates intracerebral hemorrhage-induced brain injury.J Neurotrauma. 2011 Dec;28(12):2523-34. doi: 10.1089/neu.2010.1680. Epub 2011 Oct 11. J Neurotrauma. 2011. PMID: 21988112 Free PMC article.
-
Protective role of ACE2 and its downregulation in SARS-CoV-2 infection leading to Macrophage Activation Syndrome: Therapeutic implications.Life Sci. 2020 Sep 1;256:117905. doi: 10.1016/j.lfs.2020.117905. Epub 2020 Jun 3. Life Sci. 2020. PMID: 32504757 Free PMC article. Review.
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Research Materials
Miscellaneous
