High levels of nitric oxide in individuals with pulmonary hypertension receiving epoprostenol therapy.
Lack of vasodilator substances, such as nitric oxide (NO), has been implicated in the development of pulmonary hypertension, but the pathogenesis of the disease remains speculative. We hypothesized that NO plays a role in the pathogenesis of primary pulmonary hypertension (PPH), and may serve as a sensitive and specific marker of disease progression and/or severity. To test this, exhaled NO and pulmonary artery pressure were measured in individuals with PPH and secondary pulmonary hypertension (SPH) on various therapies, including the potent vasodilator epoprostenol (prostacyclin), compared with healthy controls. NO in exhaled breath of individuals with PPH was lower than SPH or control (p<0.05). In contrast, exhaled NO of individuals with PPH or SPH receiving epoprostenol was strikingly higher than PPH or SPH individuals not receiving epoprostenol, or controls. Concomitant with higher NO levels, right ventricular systolic pressure of individuals significantly decreased with epoprostenol. Importantly, in paired measures of exhaled NO before and after epoprostenol, NO increased in all pulmonary hypertensive individuals 24 h after initiation of epoprostenol therapy (p<0.05). NO may be a useful noninvasive marker of pulmonary hypertension severity and response to prostacyclin therapy.
Ozkan
M
M
Departments of Pulmonary and Critical Care Medicine, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.
Dweik
R A
RA
Laskowski
D
D
Arroliga
A C
AC
Erzurum
S C
SC
D000293:Adolescent; D000328:Adult; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000032:analysis; D001944:Breath Tests; D011464:Epoprostenol / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000032:analysis*; D015656:Respiratory Mechanics; D014665:Vasodilator Agents / Q000032:analysis / Q000627:therapeutic use*
D000959:Antihypertensive Agents; D015415:Biomarkers; D014665:Vasodilator Agents; D009569:Nitric Oxide; D011464:Epoprostenol