Paradoxic pulmonary vasoconstriction in response to acetylcholine in patients with primary pulmonary hypertension.
Pulmonary vascular reactivity was assessed during diagnostic heart catheterization in two patients with pulmonary hypertension unexplained by pulmonary or cardiac disease and in five patients with atypical chest pain and normal coronary arteriograms. Acetylcholine, an endothelium-dependent vasodilator that also has a direct contracting effect on vascular smooth muscle cells, was infused in the right atrium in a step-wise increasing dose in order to obtain final blood concentrations in the pulmonary circulation ranging from 10(-6) mol/L to 10(-4) mol/L. In the five control patients, acetylcholine induced a dose-related decrease of pulmonary vascular resistance (-52 percent +/- 9 percent). In the patients with primary pulmonary arterial hypertension, however, acetylcholine caused a paradoxic increase of pulmonary arterial pressure and of pulmonary vascular resistance. Thus, it appears that endothelium-dependent vasodilation is impaired in the pulmonary circulation of patients with primary pulmonary arterial hypertension. Endothelial dysfunction in the pulmonary circulation may play a role in the pathophysiology of this disease.
Conraads
V M
VM
Department of Cardiology, University of Antwerp, Belgium.
Bosmans
J M
JM
Claeys
M J
MJ
Vrints
C J
CJ
Snoeck
J P
JP
De Clerck
L
L
Vermeire
P A
PA
D000109:Acetylcholine / Q000494:pharmacology*; D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000503:physiopathology*; D008168:Lung / Q000098:blood supply*; D008297:Male; D008875:Middle Aged; D014655:Vascular Resistance / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects*
D000109:Acetylcholine