{'fraction_non_alphanumeric': 0.015537600994406464, 'fraction_numerical': 0.0006215040397762585, 'mean_word_length': 5.363636363636363, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
-OONO: rebounding from nitric oxide.

Inhaled nitric oxide is an elegantly simple therapy for idiopathic pulmonary hypertension. Breathing small amounts of nitric oxide directly activates guanylyl cyclase in pulmonary resistance vessels to counteract hypertension. In patients who respond to inhaled nitric oxide, either the endogenous synthesis of nitric oxide is not sufficient to overcome the hypertensive stress or nitric oxide is being inactivated too rapidly to act on guanylate cyclase. Certainly, both processes could be operating simultaneously.

Although nitric oxide has a reputation for being highly toxic, in reality the risk of toxicity with inhaled nitric oxide is minor because nitric oxide itself is unreactive with most biological molecules and the amounts administered are low enough to minimize the formation of nitrogen dioxide. Nitric oxide becomes toxic when converted to secondary reactive nitrogen species. Nitric oxide itself is swept away from the vasculature by rapid reactions with hemoglobin. In the high oxygen environment of the lung, nitric oxide will also not significantly inhibit mitochondrial respiration. By now, many patients have been breathing nitric oxide for weeks and even months without overt harm.

However, sudden termination of inhaled nitric oxide occasionally causes a potentially life-threatening hypertensive rebound, even when treated for a few hours. Hypertensive rebound can occur in individuals who showed no initial vasodilation in response to nitric oxide. In this issue of Circulation Research , Wedgwood et al1 have shown that endothelin, the most …