Article date: February 1995
By: Jean‐Philippe Gratton, Giles A. Rae, Audrey Claing, Sabine Télémaque, Pedro D'Orléans‐Juste, in Volume 114, Issue 3, pages 720-726
In the present study, the precursors of endothelin‐1, endothelin‐2 and endothelin‐3 were tested for their pressor and bronchoconstrictor properties in the anaesthetized guinea‐pig. In addition, the effects of big‐endothelin‐1 and endothelin‐1 were assessed under urethane or ketamine/xylazine anaesthesia.
When compared to ketamine/xylazine, urethane markedly depressed the pressor and bronchoconstrictor properties of endothelin‐1 and big‐endothelin‐1.
Under ketamine/xylazine anaesthesia, the three endothelins induced a biphasic increase of mean arterial blood pressure. In contrast, big‐endothelin‐1, as well as big‐endothelin‐2 (1–38), induced only sustained increase in blood pressure whereas big‐endothelin‐3 was inactive at doses up to 25 nmol kg−1.
Big‐endothelin‐1, but not big‐endothelin‐2, induced a significant increase in airway resistance. Yet, endothelin‐1, endothelin‐2 and endothelin‐3 were equipotent as bronchoconstrictor agents.
Big‐endothelin‐1, endothelin‐1 and endothelin‐2, but not big‐endothelin‐2, triggered a marked release of prostacyclin and thromboxane A2 from the guinea‐pig perfused lung.
Our results suggest the presence of a phosphoramidon‐sensitive endothelin‐converting enzyme (ECE) which is responsible for the conversion of big‐endothelin‐1 and big‐endothelin‐2 to their active moieties, endothelin‐1 and 2. However, the lack of bronchoconstrictor and eicosanoid‐releasing properties of big‐endothelin‐2, as opposed to endothelin‐2 or big‐endothelin‐1, suggests the presence of two distinct phosphoramidon‐sensitive ECEs in the guinea‐pig. The ECE responsible for the systemic conversion of big‐endothelins possesses the same affinity for big‐endothelin‐1 and 2 but not big‐endothelin‐3. In contrast, in the pulmonary vasculature is localized in the vicinity of the sites responsible for eicosanoid release, an ECE which converts more readily big‐endothelin‐1 than big‐endothelin‐2.
In the present study, the precursors of endothelin‐1, endothelin‐2 and endothelin‐3 were tested for their pressor and bronchoconstrictor properties in the anaesthetized guinea‐pig. In addition, the effects of big‐endothelin‐1 and endothelin‐1 were assessed under urethane or ketamine/xylazine anaesthesia.
When compared to ketamine/xylazine, urethane markedly depressed the pressor and bronchoconstrictor properties of endothelin‐1 and big‐endothelin‐1.
Under ketamine/xylazine anaesthesia, the three endothelins induced a biphasic increase of mean arterial blood pressure. In contrast, big‐endothelin‐1, as well as big‐endothelin‐2 (1–38), induced only sustained increase in blood pressure whereas big‐endothelin‐3 was inactive at doses up to 25 nmol kg−1.
Big‐endothelin‐1, but not big‐endothelin‐2, induced a significant increase in airway resistance. Yet, endothelin‐1, endothelin‐2 and endothelin‐3 were equipotent as bronchoconstrictor agents.
Big‐endothelin‐1, endothelin‐1 and endothelin‐2, but not big‐endothelin‐2, triggered a marked release of prostacyclin and thromboxane A2 from the guinea‐pig perfused lung.
Our results suggest the presence of a phosphoramidon‐sensitive endothelin‐converting enzyme (ECE) which is responsible for the conversion of big‐endothelin‐1 and big‐endothelin‐2 to their active moieties, endothelin‐1 and 2. However, the lack of bronchoconstrictor and eicosanoid‐releasing properties of big‐endothelin‐2, as opposed to endothelin‐2 or big‐endothelin‐1, suggests the presence of two distinct phosphoramidon‐sensitive ECEs in the guinea‐pig. The ECE responsible for the systemic conversion of big‐endothelins possesses the same affinity for big‐endothelin‐1 and 2 but not big‐endothelin‐3. In contrast, in the pulmonary vasculature is localized in the vicinity of the sites responsible for eicosanoid release, an ECE which converts more readily big‐endothelin‐1 than big‐endothelin‐2.
DOI: 10.1111/j.1476-5381.1995.tb17198.x
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