Mitochondrial contribution to the molecular mechanism of heart acclimatization to chronic hypoxia: role of nitric oxide

10.2741/2143 ◽  
2007 ◽  
Vol 12 (1) ◽  
pp. 1247 ◽  
Author(s):  
Tamara Zaobornyj
Keyword(s):  
Nitric Oxide ◽  
Molecular Mechanism ◽  
Chronic Hypoxia

scholarly journals Important role of endothelium-dependent hyperpolarization in the pulmonary microcirculation in male mice: implications for hypoxia-induced pulmonary hypertension

2018 ◽  
Vol 314 (5) ◽  
pp. H940-H953 ◽  
Author(s):  
Shuhei Tanaka ◽  
Takashi Shiroto ◽  
Shigeo Godo ◽  
Hiroki Saito ◽  
Yosuke Ikumi ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Pulmonary Hypertension ◽  
Pulmonary Circulation ◽  
Nitrosative Stress ◽  
Chronic Hypoxia ◽  
Systemic Circulation ◽  
Physiological Conditions ◽  
Pulmonary Microcirculation ◽  
Endothelium Dependent Relaxation

Endothelium-dependent hyperpolarization (EDH) plays important roles in the systemic circulation, whereas its role in the pulmonary circulation remains largely unknown. Furthermore, the underlying mechanisms of pulmonary hypertension (PH) also remain to be elucidated. We thus aimed to elucidate the role of EDH in pulmonary circulation in general and in PH in particular. In isolated perfused lung and using male wild-type mice, endothelium-dependent relaxation to bradykinin (BK) was significantly reduced in the presence of Nω-nitro-l-arginine by ~50% compared with those in the presence of indomethacin, and the combination of apamin plus charybdotoxin abolished the residual relaxation, showing the comparable contributions of nitric oxide (NO) and EDH in the pulmonary microcirculation under physiological conditions. Catalase markedly inhibited EDH-mediated relaxation, indicating the predominant contribution of endothelium-derived H2O2. BK-mediated relaxation was significantly reduced at day 1 of hypoxia, whereas it thereafter remained unchanged until day 28. EDH-mediated relaxation was diminished at day 2 of hypoxia, indicating a transition from EDH to NO in BK-mediated relaxation before the development of hypoxia-induced PH. Mechanistically, chronic hypoxia enhanced endothelial NO synthase expression and activity associated with downregulation of caveolin-1. Nitrotyrosine levels were significantly higher in vascular smooth muscle of pulmonary microvessels under chronic hypoxia than under normoxia. A similar transition of the mediators in BK-mediated relaxation was also noted in the Sugen hypoxia mouse model. These results indicate that EDH plays important roles in the pulmonary microcirculation in addition to NO under normoxic conditions and that impaired EDH-mediated relaxation and subsequent nitrosative stress may be potential triggers of the onset of PH. NEW & NOTEWORTHY This study provides novel evidence that both endothelium-dependent hyperpolarization and nitric oxide play important roles in endothelium-dependent relaxation in the pulmonary microcirculation under physiological conditions in mice and that hypoxia first impairs endothelium-dependent hyperpolarization-mediated relaxation, with compensatory upregulation of nitric oxide, before the development of hypoxia-induced pulmonary hypertension.

A critical role of iNOS-derived Nitric Oxide (NO) and progesterone in implantation

1998 ◽  
Vol 5 (1) ◽  
pp. 115A-115A
Author(s):  
K CHWALISZ ◽  
E WINTERHAGER ◽  
T THIENEL ◽  
R GARFIELD
Keyword(s):  
Nitric Oxide ◽  
Critical Role
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