Lung cGMP release subsequent to NO inhalation in pulmonary hypertension: responders versus nonresponders.
Inhalation of nitric oxide (NO) is widely employed for the assessment of pulmonary vasoresponsiveness in pulmonary hypertension (PH). However, the reasons for the huge differences in vascular reactivity to NO between patients are unknown, and the role of NO-induced cyclic guanosine monophosphate (cGMP) is unclear. Twenty patients with severe precapillary PH were investigated. Thirty-six Swan-Ganz catheter investigations were performed and the study subjects were tested for responses to NO inhalation. This included an assessment of pulmonary and systemic arterial plasma cGMP and atrial natriuretic peptide (ANP) levels. A significant NO response (pulmonary vascular resistance (PVR) decrease >20%) was noted in nine of 20 patients (45%) during the first catheterization. A highly significant correlation between baseline plasma cGMP and ANP levels with PVR was observed (r=0.62 and r=0.66, respectively; p<0.0001). In response to NO, systemic and mixed venous cGMP levels increased from 13.9 +/- 1.28 nM and 12.75 +/- 0.99 nM to 79.23 +/- 4.99 nM and 55.25 +/- 4.41 nM (p<0.001), respectively, accompanied by the appearance of a marked transpulmonary cGMP gradient. Although in the responder group ANP levels were significantly reduced after NO inhalation, no significant correlation was observed to the extent of PVR reduction. The magnitude of the NO-elicited cGMP response did not discriminate between haemodynamic responders and nonresponders. This study concludes that plasma cyclic guanosine monophosphate levels are significantly correlated with the severity of disease in pulmonary arterial hypertension. Nitric oxide inhalation provokes a prompt increase in cyclic guanosine monophosphate secretion, but the magnitude of this release is not linked with a decrease in pulmonary vascular resistance.
Ghofrani
H A
HA
Dept of Internal Medicine, Medical Clinic II, Justus-Liebig-University, Giessen, Germany. Ardeschir.Ghofrani@innere.med.uni-giessen.de
Wiedemann
R
R
Rose
F
F
Weissmann
N
N
Schermuly
R T
RT
Quanz
K
K
Grimminger
F
F
Seeger
W
W
Olschewski
H
H
D000280:Administration, Inhalation; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D002407:Catheterization, Swan-Ganz; D006152:Cyclic GMP / Q000097:blood*; D006801:Humans; D006976:Hypertension, Pulmonary / Q000378:metabolism / Q000628:therapy*; D008168:Lung / Q000378:metabolism*; D008875:Middle Aged; D009569:Nitric Oxide / Q000008:administration & dosage* / Q000627:therapeutic use; D014655:Vascular Resistance / Q000187:drug effects; D014665:Vasodilator Agents / Q000008:administration & dosage* / Q000627:therapeutic use
D014665:Vasodilator Agents; D009569:Nitric Oxide; D006152:Cyclic GMP