Sacubitril/valsartan treatment relieved the progression of established pulmonary hypertension in rat model and its mechanism
| Autor: | Ya Wang, Shuai Lu, WenHu Liu, Zhaohui Wang, Xiaohui Zeng, Shuangye Liu, Yan Wang, Jing Hu |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Male
0301 basic medicine medicine.drug_class Hypertension Pulmonary Tetrazoles Pharmacology 030226 pharmacology & pharmacy General Biochemistry Genetics and Molecular Biology Sacubitril Rats Sprague-Dawley Angiotensin Receptor Antagonists 03 medical and health sciences 0302 clinical medicine Renin–angiotensin system medicine Natriuretic peptide Animals General Pharmacology Toxicology and Pharmaceutics Hypoxia Receptor Monocrotaline Angiotensin II receptor type 1 business.industry Aminobutyrates Biphenyl Compounds Body Weight General Medicine medicine.disease Pulmonary hypertension Rats Disease Models Animal Drug Combinations 030104 developmental biology Valsartan Disease Progression business Sacubitril Valsartan medicine.drug |
| Zdroj: | Life Sciences. 266:118877 |
| ISSN: | 0024-3205 |
| DOI: | 10.1016/j.lfs.2020.118877 |
| Popis: | Pulmonary hypertension (PH) is a fatal disease identified by progressive elevated pulmonary arterial pressure, which neurohormonal activation is a notable contributor to its development. Sacubitril/valsartan is a complex of sacubitril [via enhancing the natriuretic peptide (NP) system] and valsartan [via blocking the renin-angiotensin-aldosterone system (RAAS)]. Regulation of the two neurohormonal system had been shown to attenuate PH. This study was to explore the role of sacubitril/valsartan in both monocrotaline (MCT)-induced and hypoxia-induced rat models and the underlying mechanism.The rats were treated with MCT or hypoxic environment for 14 days, after that sacubitril/valsartan were given for another 14 days. Hemodynamic measurements and histological assessments were performed. The expression of NPs was measured using RT-PCR and ELISA, while the protein level of natriuretic peptide receptors (NPRs) and AT1 receptor were detected by western blot, the concentrations of cGMP, IL-1β, IL-6, TNF-α and TGF-β1 were tested by ELISA.We found that sacubitril/valsartan significantly improved the hemodynamic and histological data of two PH models. Sacubitril/valsartan suppressed the protein expression of AT1 receptor (P 0.05). The intervention increased the expression of ANP and CNP (P 0.05) and therefore upregulated the protein expression of NPRs (P 0.05), raised the concentration of cGMP (P 0.05). In addition, the treatment reduced the concentration of IL-1β, IL-6 and TNF-α (P 0.05) but have no effects on TGF-β1.Sacubitril/valsartan alleviated PH in MCT-induced and hypoxia-induced rat models by inhibiting the activated RAAS, promoting ANP/NPR-A/cGMP and CNP/NPR-B/cGMP pathway, restoring the NPR-C signaling and the anti-inflammatory effects. |
| Databáze: | OpenAIRE |
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