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Spasmolytic effects of colforsin daropate on serotonin‐induced pulmonary hypertension and bronchoconstriction in dogs
Author(s) -
Hirota K.,
Yoshioka H.,
Kabara S.,
Koizumi Y.,
Abe H.,
Sato T.,
Matsuki A.
Publication year - 2002
Publication title -
acta anaesthesiologica scandinavica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.738
H-Index - 107
eISSN - 1399-6576
pISSN - 0001-5172
DOI - 10.1034/j.1399-6576.2002.t01-1-460312.x
Subject(s) - bronchoconstriction , medicine , vascular resistance , propranolol , pulmonary hypertension , serotonin , anesthesia , endocrinology , vasodilation , blood pressure , asthma , receptor
Background: We have previously found that agents increasing intracellular cAMP levels of smooth muscles, such as PDE3 inhibitors, aminophylline and prostaglandin E 1 , produce both bronchodilation and pulmonary vasodilation in serotonin‐induced pulmonary hypertension and bronchoconstriction models. In the present study we have simultaneously evaluated the spasmolytic effects of colforsin daropate, a novel forskolin derivative, on serotonin‐induced pulmonary hypertension and bronchoconstriction. Methods: Ten mongrel dogs were anesthetized with pentobarbital. The pulmonary hypertension and bronchoconstriction were elicited with serotonin (10 µg/kg + 1 mg·kg −1 ·h −1 ) and assessed as percentage changes in pulmonary vascular resistance (PVR) and bronchial cross‐sectional area (BCA) (basal = 100%). Initially, the relaxant effects of colforsin daropate (0–300 µg/kg) were determined. The PVR and BCA were assessed before and 30 min after serotonin infusion began and 5 min after each dose of colforsin daropate. To determine whether colforsin daropate‐induced relaxation is independent of plasma catecholamine, propranolol 0.4 mg/kg was given following colforsin daropate 300 µg/kg i.v. Results: Colforsin daropate reversed both pulmonary hypertension and bronchoconstriction dose‐dependently: ‐logED 50 (95% confidence intervals, mean ED 50 ) for pulmonary hypertension and bronchoconstriction 5.44 (5.08–5.80, 3.6 µg/kg) and 4.90 (4.06–5.20, 12.5 µg/kg), respectively. However, colforsin daropate (≥ 30 µg/kg) produced a more pronounced systemic than pulmonary vasodilation. Although colforsin daropate (≥ 30 µg/kg) significantly increased plasma catecholamines, propranolol did not reverse the relaxant effects. Conclusions: Colforsin daropate may attenuate bronchoconstriction and pulmonary hypertension. In addition, as β‐blockade did not change the attenuation, the relaxant effects may be independent of plasma catecholamines.