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Evaluation of bosentan, pinacidil and nitroprusside on human pulmonary arteries: comparison with rat pulmonary arteries *
Author(s) -
Wanstall JC,
Kay CS,
O'Donnell SR,
Wilson K,
Cole PH,
Matar K
Publication year - 1997
Publication title -
fundamental and clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.655
H-Index - 73
eISSN - 1472-8206
pISSN - 0767-3981
DOI - 10.1111/j.1472-8206.1997.tb00864.x
Subject(s) - bosentan , pulmonary artery , medicine , endothelin receptor , cardiology , pinacidil , artery , endothelin 1 , anesthesia , endocrinology , receptor , glibenclamide , diabetes mellitus
Summary— Bosentan (endothelin ET A /ET B antagonist), pinacidil (potassium channel opener) and nitroprusside (nitric oxide donor) were examined on isolated ring preparations of human intralobar pulmonary artery (3rd‐5th generation; internal radius > 1 mm), rat main pulmonary artery (1st generation; internal radius > 1 mm) and rat intralobar pulmonary artery (3rd generation; internal radius ≥ 0.1–0.3 mm). The potency of endothelin‐1 was the same in all three artery types. In human intralobar artery and rat main pulmonary artery, bosentan (3 and 10 μM) shifted the endothelin‐1 concentration response curve to a higher concentration range (endothelin‐1 concentration ratios, in human intralobar and rat main pulmonary artery, respectively: 3 liM bosentan, 4.5 and 8.1; 10 /xM bosentan, 13.5 and 19.5), but caused no significant block of endothelin‐1 in rat intralobar artery. The latter finding may be due to the reported presence of ET B receptors in rat intralobar arteries and the higher potency of bosentan on ET A than on ET B receptors. In contrast, the potencies of nitroprusside and pinacidil (relaxation of submaximal contractions to the thromboxane‐mimetic, U46619) agreed on human and rat intralobar arteries but were 6 to 16‐fold lower than on rat main pulmonary artery. We conclude that data obtained on pulmonary arteries from rats can be useful in predicting the effects of vasoactive drugs in human pulmonary arteries but selection of the most appropriate rat artery for study will depend on the drug group under investigation. For potassium channel openers and nitric oxide donors, good agreement between human and rat data will be found when using pulmonary arteries from the same anatomical location even though they differ markedly in size. In contrast, for endothelin antagonists, agreement is more likely to be found in arteries of comparable size, despite their different anatomical locations.