Angiotensin II AT1 receptor alters ACE2 activity, eNOS expression and CD44-hyaluronan interaction in rats with hypertension and myocardial fibrosis

Autor: Li-Hui Zhang, Ning-Ping Wang, Feng Bai, Zhi-Qing Zhao, R E Garner, Robert J. McKallip, Xue-Fen Pang
Rok vydání: 2016
Předmět:
Male
0301 basic medicine
Angiotensin receptor
medicine.medical_specialty
Nitric Oxide Synthase Type III
Cardiac fibrosis
Peptidyl-Dipeptidase A
030204 cardiovascular system & hematology
Receptor
Angiotensin
Type 1
General Biochemistry
Genetics and Molecular Biology
Rats
Sprague-Dawley
03 medical and health sciences
0302 clinical medicine
Enos
Internal medicine
medicine
Animals
Hyaluronic Acid
General Pharmacology
Toxicology and Pharmaceutics
Angiotensin II receptor type 1
biology
Chemistry
Angiotensin-converting enzyme
General Medicine
medicine.disease
biology.organism_classification
Angiotensin II
Rats
Hyaluronan Receptors
030104 developmental biology
Endocrinology
Hypertension
Angiotensin-converting enzyme 2
cardiovascular system
biology.protein
Angiotensin-Converting Enzyme 2
Telmisartan
Cardiomyopathies
hormones
hormone substitutes
and hormone antagonists
medicine.drug
Zdroj: Life Sciences. 153:141-152
ISSN: 0024-3205
DOI: 10.1016/j.lfs.2016.04.013
Popis: This study tested the hypothesis that angiotensin II (Ang II) AT1 receptor is involved in development of hypertension and cardiac fibrosis via modifying ACE2 activity, eNOS expression and CD44-hyaluronan interaction.Male Sprague-Dawley rats were subjected to Ang II infusion (500ng/kg/min) using osmotic minipumps up to 4weeks and the AT1 receptor blocker, telmisartan was administered by gastric gavage (10mg/kg/day) during Ang II infusion.Our results indicated that Ang II enhances AT1 receptor, downregulates AT2 receptor, ACE2 activity and eNOS expression, and increases CD44 expression and hyaluronidase activity, an enzyme for hyaluronan degradation. Further analyses revealed that Ang II increases blood pressure and augments vascular/interstitial fibrosis. Comparison of the Ang II group, treatment with telmisartan significantly increased ACE2 activity and eNOS expression in the intracardiac vessels and intermyocardium. These changes occurred in coincidence with decreased blood pressure. Furthermore, the locally-expressed AT1 receptor was downregulated, as evidenced by an increased ratio of the AT2 over AT1 receptor (1.4±0.4% vs. 0.4±0.1% in Ang II group, P0.05). Along with these modulations, telmisartan inhibited membrane CD44 expression and hyaluronidase activity, decreased populations of macrophages and myofibroblasts, and reduced expression of TGFβ1 and Smads. Collagen I synthesis and tissue fibrosis were attenuated as demonstrated by the less extensive collagen-rich area.These results suggest that the AT1 receptor is involved in development of hypertension and cardiac fibrosis. Selective activating ACE2/eNOS and inhibiting CD44/HA interaction might be considered as the therapeutic targets for attenuating Ang II induced deleterious cardiovascular effects.
Databáze: OpenAIRE
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