肺高血圧症ラット肺動脈の薬理学的研究 : 血管作動物質に対する反応様式

Abstract

The intraperitoneal injection of monocrotaline, a pyrrolizidine alkaloid derived from Crotalaria spectabilis, to young rats induced pulmonary hypertension. The present investigation explored the functional changes in pulmonary arteries of pulmonary hypertensive rats. Noradrenaline and tyramine caused a dose-dependent contractions of helically-cut strips of the pulmonary arteries. Median effective concentrations of these agents were not altered by pretreatment of rats with monocrotaline. Maximal tension developed by noradrenaline and tension developed by K^+30mM were not altered by pretreatment of rats with monocrotaline, but developed tension per unit cross-sectional area of the helically-cut strips of the monocrotaline-treated rats decreased significantly. Histamine, adenosine and isoproterenol relaxed the arteries contracted with prostaglandin F_<2α>. The relaxant effect of isoproterenol and adenosine was attenuated in arteries from rats pretreated with monocrotaline, while histamine-induced relaxation was not affected by pretreatment with monocrotaline. In summary, these results were concluded. 1) Sensitivity of β-adrenergic and adenosine receptors may be involved in the development and maintenance of the hypertension. 2) Sensitivity of α-adrenergic receptors and augmented release of noradrenaline from adrenergic nerves are not involved in the development and maintenance of hypertension.