Biomaterial Database

Protection from pulmonary hypertension with an orally active endothelin receptor antagonist in hypoxic rats. 1995

S Eddahibi, and B Raffestin, and M Clozel, and M Levame, and S Adnot

Département de Physiologie, Centre Hospitalier Universitaire Henri Mondor, Créteil, France.

The aim of this study was to investigate the potential role of endothelin (ET) in the development of chronic hypoxic pulmonary hypertension. Pulmonary vascular reactivity to ET-1 was first examined in isolated perfused lungs from normoxic and chronically hypoxic rats in the presence of bosentan, a new nonpeptide mixed antagonist of ETA and ETB receptors. The effect of chronic treatment with bosentan was then examined in rats that were exposed to chronic hypoxia and developed pulmonary hypertension. In lungs from normoxic rats, bosentan (10(-5) M) abolished the vasodilator responses to ET-1 (10(-10) M) or to the ETB-selective agonist IRL-1620 (10(-10) M) and attenuated the vasoconstrictor responses to 10(-9) M ET-1 (from 8.7 +/- 0.7 to 1.8 +/- 0.3 mmHg, P < 0.01) or 10(-9) M IRL-1620 (from 1.5 +/- 0.4 to 0.4 +/- 0.1 mmHg, P < 0.05). In lungs from chronically hypoxic rats, the pressor response to 3 x 10(-10) M ET-1 was abolished by bosentan and partially reduced by the selective ETA antagonist BQ-123. In conscious rats previously exposed to hypoxia for 15 days, pretreatment with bosentan (100 mg.kg-1.day-1 by gavage) for 3 days attenuated the increase in systemic arterial pressures and the concomitant decrease of cardiac output in response to an intravenous bolus of ET-1 (3 x 10(-10) M). In rats exposed to hypoxia for 15 days and simultaneously treated with bosentan, pulmonary arterial pressure was lower (P < 0.05) and right ventricular hypertrophy was less severe (P < 0.01) than in control hypoxic rats treated with vehicle.(ABSTRACT TRUNCATED AT 250 WORDS)

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
D002908	Chronic Disease	Diseases which have one or more of the following characteristics: they are permanent, leave residual disability, are caused by nonreversible pathological alteration, require special training of the patient for rehabilitation, or may be expected to require a long period of supervision, observation, or care (Dictionary of Health Services Management, 2d ed). For epidemiological studies chronic disease often includes HEART DISEASES; STROKE; CANCER; and diabetes (DIABETES MELLITUS, TYPE 2).	Chronic Condition,Chronic Illness,Chronically Ill,Chronic Conditions,Chronic Diseases,Chronic Illnesses,Condition, Chronic,Disease, Chronic,Illness, Chronic
D006439	Hemodynamics	The movement and the forces involved in the movement of the blood through the CARDIOVASCULAR SYSTEM.	Hemodynamic
D000077300	Bosentan	A sulfonamide and pyrimidine derivative that acts as a dual endothelin receptor antagonist used to manage PULMONARY HYPERTENSION and SYSTEMIC SCLEROSIS.	4-t-Butyl-N-(6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)-2,2'-bipyrimidin-4-yl)benzenesulfonamide,Bosentan Anhydrous,Bosentan Monohydrate,Ro 47-0203,Ro-47-0203,Tracleer,Ro 47 0203,Ro 470203
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
D000860	Hypoxia	Sub-optimal OXYGEN levels in the ambient air of living organisms.	Anoxia,Oxygen Deficiency,Anoxemia,Deficiency, Oxygen,Hypoxemia,Deficiencies, Oxygen,Oxygen Deficiencies
D013449	Sulfonamides	A group of compounds that contain the structure SO2NH2.	Sulfonamide,Sulfonamide Mixture,Sulfonamide Mixtures,Mixture, Sulfonamide,Mixtures, Sulfonamide
D016232	Endothelins	21-Amino-acid peptides produced by vascular endothelial cells and functioning as potent vasoconstrictors. The endothelin family consists of three members, ENDOTHELIN-1; ENDOTHELIN-2; and ENDOTHELIN-3. All three peptides contain 21 amino acids, but vary in amino acid composition. The three peptides produce vasoconstrictor and pressor responses in various parts of the body. However, the quantitative profiles of the pharmacological activities are considerably different among the three isopeptides.	Endothelium-Derived Vasoconstrictor Factors,Endothelin,Vasoconstrictor Factors, Endothelium-Derived
D017208	Rats, Wistar	A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.	Wistar Rat,Rat, Wistar,Wistar Rats