Spasmolytic effects of colforsin daropate on serotonin-induced pulmonary hypertension and bronchoconstriction in dogs.

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Hirota K, Yoshioka H, Kabara S, Koizumi Y, Abe H, Sato T, Matsuki A

Spasmolytic effects of colforsin daropate on serotonin-induced pulmonary hypertension and bronchoconstriction in dogs.

Acta Anaesthesiol Scand. 2002 Mar;46(3):297-302.

PubMed ID

11939921 [ View in PubMed

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Abstract

BACKGROUND: We have previously found that agents increasing intracellular cAMP levels of smooth muscles, such as PDE3 inhibitors, aminophylline and prostaglandin E1, 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 microg/kg + 1 mg x kg(-1) x 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 microg/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 microg/kg i.v. RESULTS: Colforsin daropate reversed both pulmonary hypertension and bronchoconstriction dose-dependently: -logED50 (95% confidence intervals, mean ED50) for pulmonary hypertension and bronchoconstriction 5.44 (5.08-5.80, 3.6 microg/kg) and 4.90 (4.06-5.20, 12.5 microg/kg), respectively. However, colforsin daropate (>or= 30 microg/kg) produced a more pronounced systemic than pulmonary vasodilation. Although colforsin daropate (>or= 30 microg/kg) significantly increased plasma catecholamines, propranolol did not reverse the relaxant effects. CONCLUSIONS: Colforsin daropate may attenuate bronchoconstriction and pulmonary hypertension. In addition, as beta-blockade did not change the attenuation, the relaxant effects may be independent of plasma catecholamines.

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Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Aminophylline	cGMP-inhibited 3',5'-cyclic phosphodiesterase A	Protein	Humans	Yes	Inhibitor	Details