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Inhibition of Nitric Oxide (NO) Alone Does Not Lead to the Development of Pulmonary Arterial Hypertension (PAH) in Rats.
Author(s) -
Sun Xiaowei,
Ku David D.
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.933.11
Subject(s) - medicine , pulmonary hypertension , nitric oxide , phenylephrine , right ventricular hypertrophy , bolus (digestion) , lung , cardiology , agonist , heart failure , blood pressure , receptor
PAH is a deadly lung disorder that often leads to right ventricular hypertrophy (RVH) and heart failure, but the exact role of NO is not well understood. We found that an acute bolus injection of 10 mg/kg L‐NAME or chronic (1 to 2 weeks) treatment in rats resulted in a sustained systemic hypertension, while the pulmonary pressure (PP) was surprisingly unchanged. Intravenous administration of bolus phenylephrine (PE, an α receptor agonist) also resulted in a marked increase in the systemic pressure, but not PP. However, following L‐NAME treatment or induction of monocrotaline (MCT)‐induced PAH this same PE resulted in a marked increase in PulP response, suggesting an important NO modulatory role on basal pulmonary vasoreactivity. Indeed, we found that L‐NAME pretreatment markedly accelerated the development of MCT‐induced PAH and RVH in the rats. Taken together, these results demonstrate that pulmonary endothelial NO production plays an important modulatory role on pulmonary circulation and reactivity, but not the most dominating role as it is in the systemic circulation. Prior inhibition of pulmonary endothelial NO production could accelerate the development of PAH, RVH and heart failure. Further studies using NO and its donor to prevent and treat the deadly PAH disease and preservation of RV function are currently under investigation.