[Protective effects of beraprost plus simvastatin on monocrotaline-induced pulmonary arterial hypertension in rats]. 2013

Sheng-hao Wang, and Shuang Liu, and Jing-hua Yang, and Zeng-zhi Wang, and Jie Li, and Wei-wei Hou
Department of Infection Diseases, Affiliated Beijing Anzhen Hospital, Capital Medical University & Beijing Institute of Heart, Lung & Blood Vessel Diseases, Beijing 100029, China.

OBJECTIVE To explore the protective effects of beraprost plus simvastatin on monocrotaline-induced pulmonary arterial hypertension in rats. METHODS Forty male Sprague-Dawley rats were allocated to control (C), untreated pulmonary arterial hypertension (P), beraprost (B), simvastatin (S) and combination groups (Com) (n = 8 each). Normal saline was injected subcutaneously into group C and then there was no other intervention for 21 days. Group P, B, S and Com rats received subcutaneous injections of monocrotaline (MCT, 60 mg/kg) and then isovolumetric normal saline, beraprost (100 µg·kg(-1)·d(-1)), simvastatin (2 mg·kg(-1)·d(-1)) and beraprost (100 µg·kg(-1)·d(-1)) plus simvastatin (2 mg·kg(-1)·d(-1)) by daily gastric lavage for 21 days. At Day 22, heart rate (HR), mean arterial pressure (MAP) and mean pulmonary pressure (mPAP) were detected and right heart ventricular hypertrophy index (RVHI) was calculated. The histopathology changes and tunica media thickness percentage of pulmonary arteries (WT%) were evaluated by pulmonary tissue staining. The results were analyzed statistically. RESULTS The differences of HR and MAP were not significant among 5 groups (all P > 0.05). The levels of mPAP, RVHI and WT% in group B ((27.4 ± 3.7) mm Hg, 0.35 ± 0.03, 26.7% ± 2.4%), group S ((29.9 ± 4.4) mm Hg, 0.36 ± 0.03, 28.2% ± 1.9%) and group Com ((23.1 ± 3.9) mm Hg, 0.32 ± 0.03, 17.4% ± 3.3%) were lower than those in group P ((35.4 ± 5.7) mm Hg, 0.41 ± 0.05, 42.8% ± 5.9%) (all P < 0.05). CONCLUSIONS The combined use of beraprost and simvastatin may delay the increase of mPAP and remodeling of pulmonary vessels and inhibit right ventricular hypertrophy in pulmonary arterial hypertension rats. Its efficacy is superior to that of monotherapy.

UI MeSH Term Description Entries
D006976 Hypertension, Pulmonary Increased VASCULAR RESISTANCE in the PULMONARY CIRCULATION, usually secondary to HEART DISEASES or LUNG DISEASES. Pulmonary Hypertension
D008297 Male Males
D011464 Epoprostenol A prostaglandin that is a powerful vasodilator and inhibits platelet aggregation. It is biosynthesized enzymatically from PROSTAGLANDIN ENDOPEROXIDES in human vascular tissue. The sodium salt has been also used to treat primary pulmonary hypertension (HYPERTENSION, PULMONARY). Prostacyclin,Prostaglandin I2,Epoprostanol,Epoprostenol Sodium,Epoprostenol Sodium Salt, (5Z,9alpha,11alpha,13E,15S)-Isomer,Flolan,Prostaglandin I(2),Veletri
D004359 Drug Therapy, Combination Therapy with two or more separate preparations given for a combined effect. Combination Chemotherapy,Polychemotherapy,Chemotherapy, Combination,Combination Drug Therapy,Drug Polytherapy,Therapy, Combination Drug,Chemotherapies, Combination,Combination Chemotherapies,Combination Drug Therapies,Drug Polytherapies,Drug Therapies, Combination,Polychemotherapies,Polytherapies, Drug,Polytherapy, Drug,Therapies, Combination Drug
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D016686 Monocrotaline A pyrrolizidine alkaloid and a toxic plant constituent that poisons livestock and humans through the ingestion of contaminated grains and other foods. The alkaloid causes pulmonary artery hypertension, right ventricular hypertrophy, and pathological changes in the pulmonary vasculature. Significant attenuation of the cardiopulmonary changes are noted after oral magnesium treatment. Monocrotaline Hydrochloride (13alpha,14alpha)-Isomer,Monocrotaline, (all-xi)-Isomer
D017207 Rats, Sprague-Dawley A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company. Holtzman Rat,Rats, Holtzman,Sprague-Dawley Rat,Rats, Sprague Dawley,Holtzman Rats,Rat, Holtzman,Rat, Sprague-Dawley,Sprague Dawley Rat,Sprague Dawley Rats,Sprague-Dawley Rats
D051381 Rats The common name for the genus Rattus. Rattus,Rats, Laboratory,Rats, Norway,Rattus norvegicus,Laboratory Rat,Laboratory Rats,Norway Rat,Norway Rats,Rat,Rat, Laboratory,Rat, Norway,norvegicus, Rattus
D019821 Simvastatin A derivative of LOVASTATIN and potent competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HYDROXYMETHYLGLUTARYL COA REDUCTASES), which is the rate-limiting enzyme in cholesterol biosynthesis. It may also interfere with steroid hormone production. Due to the induction of hepatic LDL RECEPTORS, it increases breakdown of LDL CHOLESTEROL. MK-733,Synvinolin,Zocor,MK 733,MK733

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