Tjen-A-Looi S, Ekman R, Osborn J, Keith I
Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin-Madison 53706, USA.
Am J Physiol. 1996 Dec;271(6 Pt 2):H2246-53. doi: 10.1152/ajpheart.1996.271.6.H2246.
The role of endothelin (ET)-1 in pulmonary arterial pressure (Ppa) homeostasis and hypoxia-induced pulmonary hypertension was examined. ET-1 was chronically infused (2 and 4 pmol.kg-1.min-1) into the pulmonary circulation of male Sprague-Dawley rats for 3, 7, and 14 days while they were exposed to normoxia or hypobaric hypoxia (inspired O2 fraction 10%). The role of endogenous ET was examined by infusion of ET antiserum (ET-AS; 0.25 and 0.5 microliter.rat-1.h-1; cross-reacting with ET-1, -2, and -3) or the ETA-receptor blocker BQ-123 (10 pmol.kg-1.min-1). ET-1 (4 pmol) increased Ppa at 3 and 7 days in normoxia and hypoxia and was ineffective at 14 days, probably from ETA-receptor downregulation. BQ-123 blunted the hypoxic Ppa rise at all times, confirming a role for ETA receptors. ET-AS (0.5 microliter) was mostly ineffective but exacerbated hypoxic Ppa at 14 days, in contrast to BQ-123, suggesting that a different ET receptor could be involved. ET-1 infusion (2 pmol) caused right ventricular hypertrophy (RVH) in normoxia and exacerbated RVH in hypoxia, whereas BQ-123 and ET-AS (0.25 microliter) reduced hypoxic RVH. In conclusion, endogenous ET-1 plays a role in hypoxia-induced pulmonary hypertension and RVH by augmenting the level of hypoxic response. ET-1 also affects hematocrit and may reduce blood levels of the vasodilator calcitonin gene-related peptide.
研究了内皮素（ET）-1在肺动脉压（Ppa）稳态及低氧诱导的肺动脉高压中的作用。将ET-1以2和4 pmol·kg⁻¹·min⁻¹的剂量长期输注到雄性Sprague-Dawley大鼠的肺循环中，持续3、7和14天，同时让它们暴露于常氧或低压低氧环境（吸入氧分数为10%）。通过输注ET抗血清（ET-AS；0.25和0.5微升·大鼠⁻¹·小时⁻¹；与ET-1、-2和-3交叉反应）或ETA受体阻滞剂BQ-123（10 pmol·kg⁻¹·min⁻¹）来研究内源性ET的作用。在常氧和低氧条件下，ET-1（4 pmol）在3天和7天时可使Ppa升高，而在14天时无效，这可能是由于ETA受体下调所致。BQ-123在所有时间均能减弱低氧引起的Ppa升高，证实了ETA受体的作用。ET-AS（0.5微升）大多无效，但在14天时会加剧低氧引起的Ppa升高，这与BQ-123相反，提示可能涉及不同的ET受体。输注ET-1（2 pmol）在常氧条件下可导致右心室肥厚（RVH），并在低氧时加剧RVH，而BQ-123和ET-AS（0.25微升）可减轻低氧引起的RVH。总之，内源性ET-1通过增强低氧反应水平在低氧诱导的肺动脉高压和RVH中起作用。ET-1还会影响血细胞比容，并可能降低血管舒张剂降钙素基因相关肽的血药浓度。
