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(Circulation. 1995;92:114-119.)
© 1995 American Heart Association, Inc.

Articles

Role of Endothelin-1 in Beagles With Dehydromonocrotaline-Induced Pulmonary Hypertension

Morihito Okada, MD; Chojiro Yamashita, MD; Masayoshi Okada, MD; Kenji Okada, MD

From the Department of Surgery, Division II, Kobe University School of Medicine, Kobe, Japan.

Correspondence to Morihito Okada, MD, Department of Surgery, Division II, Kobe University School of Medicine, Kusunoki-cho 7-5-2, Chuo-ku, 650 Kobe City, Japan.

Background Although plasma levels of endothelin-1 (ET-1) increase in patients with pulmonary hypertension (PH), its role in PH is unknown. We investigated the contribution of endogenous ET-1 to cardiopulmonary changes in beagles with dehydromonocrotaline (DMCT)-induced PH.

Methods and Results Eight 3-month-old beagles were given a single injection of 3 mg/kg DMCT via the right atrium. During the 8 weeks after injection, the mean pulmonary arterial pressure (PAP) and plasma ET-1 level increased significantly from 11.6±2.3 to 35.9±7.1 mm Hg and from 1.24±0.25 to 3.25±0.94 pg/mL, respectively. In controls, ET-1 infusion elevated the systemic arterial pressure (SAP) but did not alter PAP. In PH beagles, ET-1 infusion increased SAP, which was attenuated by FR139317 (an endothelin type [ET] A receptor antagonist), and produced a dose-dependent decrease in PAP, which was attenuated by RES-701-1 (an ETB receptor antagonist). In PH beagles, FR139317 infusion decreased PAP, and RES-701-1 infusion increased PAP. Sarafotoxin S6c (an ETB agonist) infusion decreased PAP in PH beagles.

Conclusions These results suggest that endogenous ET-1 is elevated in PH disease and may mitigate PH by acting on ETB receptors.

Key Words: pulmonary heart disease • endothelin

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