Hypoxia-Induced Pulmonary Injury-Adrenergic Blockade Attenuates Nitrosative Stress, and Proinflammatory Cytokines but Not Pulmonary Edema.

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.

Effects of Normobaric Hypoxia and Adrenergic Blockade over 72 h on Cardiac Function in Rats.

In rats, acute normobaric hypoxia depressed left ventricular (LV) inotropic function. After 24 h of hypoxic exposure, a slight recovery of LV function occurred. We speculated that prolonged hypoxia (72 h) would induce acclimatization and, hence, recovery of LV function. Moreover, we investigated biomarkers of nitrosative stress and apoptosis as possible causes of hypoxic LV depression. To elucidate the role of hypoxic sympathetic activation, we studied whether adrenergic blockade would further deteriorate the general state of the animals and their cardiac function. Ninety-four rats were exposed over 72 h either to normal room air (N) or to normobaric hypoxia (H). The rodents received infusion (0.1 mL/h) with 0.9% NaCl or with different adrenergic blockers. Despite clear signs of acclimatization to hypoxia, the LV depression continued persistently after 72 h of hypoxia. Immunohistochemical analyses revealed significant increases in markers of nitrosative stress, adenosine triphosphate deficiency and apoptosis in the myocardium, which could provide a possible explanation for the absence of LV function recovery. Adrenergic blockade had a slightly deteriorative effect on the hypoxic LV function compared to the hypoxic group with maintained sympathetic efficacy. These findings show that hypoxic sympathetic activation compensates, at least partially, for the compromised function in hypoxic conditions, therefore emphasizing its importance for hypoxia adaptation.