Riha Isabel, Salameh Aida, Hoschke Annekathrin, Raffort Coralie, Koedel Julia, Rassler Beate
Carl-Ludwig-Institute of Physiology, University of Leipzig, 04103 Leipzig, Germany.
Department of Pediatric Cardiology, Heart Centre, University of Leipzig, 04289 Leipzig, Germany.
J Cardiovasc Dev Dis. 2024 Jun 27;11(7):195. doi: 10.3390/jcdd11070195.
Hypoxia can induce pulmonary edema (PE) and inflammation. Furthermore, hypoxia depresses left ventricular (LV) inotropy despite sympathetic activation. To study the role of hypoxic sympathetic activation, we investigated the effects of hypoxia with and without adrenergic blockade (AB) on cardiovascular dysfunction and lung injury, i.e., pulmonary edema, congestion, inflammation, and nitrosative stress. Eighty-six female rats were exposed for 72 h to normoxia or normobaric hypoxia and received infusions with NaCl, prazosin, propranolol, or prazosin-propranolol combination. We evaluated hemodynamic function and performed histological and immunohistochemical analyses of the lung. Hypoxia significantly depressed LV but not right ventricular (RV) inotropic and lusitropic functions. AB significantly decreased LV function in both normoxia and hypoxia. AB effects on RV were weaker. Hypoxic rats showed signs of moderate PE and inflammation. This was accompanied by elevated levels of tumor necrosis factor α (TNFα) and nitrotyrosine, a marker of nitrosative stress in the lungs. In hypoxia, all types of AB markedly reduced both TNFα and nitrotyrosine. However, AB did not attenuate PE. The results suggest that hypoxia-induced sympathetic activation contributes to inflammation and nitrosative stress in the lungs but not to PE. We suggest that AB in hypoxia aggravates hypoxia-induced inotropic LV dysfunction and backlog into the pulmonary circulation, thus promoting PE.
缺氧可诱发肺水肿（PE）和炎症。此外，尽管交感神经激活，但缺氧会降低左心室（LV）的收缩力。为研究缺氧时交感神经激活的作用，我们研究了有无肾上腺素能阻断（AB）的缺氧对心血管功能障碍和肺损伤（即肺水肿、充血、炎症和亚硝化应激）的影响。86只雌性大鼠暴露于常氧或常压缺氧环境72小时，并接受氯化钠、哌唑嗪、普萘洛尔或哌唑嗪 - 普萘洛尔组合的输注。我们评估了血流动力学功能，并对肺进行了组织学和免疫组化分析。缺氧显著降低左心室而非右心室（RV）的收缩和舒张功能。AB在常氧和缺氧状态下均显著降低左心室功能。AB对右心室的影响较弱。缺氧大鼠表现出中度PE和炎症迹象。这伴随着肿瘤坏死因子α（TNFα）水平升高以及硝基酪氨酸（肺中亚硝化应激的标志物）升高。在缺氧状态下，所有类型的AB均显著降低TNFα和硝基酪氨酸。然而，AB并未减轻PE。结果表明，缺氧诱导的交感神经激活导致肺中的炎症和亚硝化应激，但不导致PE。我们认为，缺氧时的AB会加重缺氧诱导的左心室收缩功能障碍并导致肺循环淤血，从而促进PE。
