Impairment of endothelium-dependent pulmonary vasodilation in patients with primary pulmonary hypertension.
BACKGROUND
Pulmonary vascular tone may be modulated by endothelium-derived vasoactive mediators. Endothelial dysfunction is thought to occur in primary pulmonary hypertension. The aim of this study was to evaluate the vascular responses of patients with severe primary pulmonary hypertension to endothelium-dependent vasodilators (for example, substance P) and non-endothelium-dependent vaasodilators (for example, adenosine).


METHODS
Six patients with primary pulmonary hypertension (mean (SE) systolic, diastolic, and pulmonary artery pressures 91.1 (7), 45.2 (3), and 62 (4.2) mm Hg, respectively, and baseline total pulmonary vascular resistance (TPVR) 1949 (164) dynes.s.cm-5) underwent sequential infusions of substance P (5-100 pmol/min) and adenosine (5-50 micrograms/kg/min) in random order. Pulmonary and systemic haemodynamics were monitored by indwelling radial and pulmonary arterial catheters.


RESULTS
Substance P caused a marked fall in systemic vascular resistance (SVR) but minimal pulmonary vasodilation (mean maximal percentage change from baseline in TPVR:SVR ratio 27.85 (6.5)%, p < 0.01). Adenosine caused TPVR to fall, but resulted in no change in SVR (mean maximum percentage change from baseline in TPVR:SVR ratio -9.85 (3.5)%, p < 0.05).


CONCLUSIONS
Endothelium-dependent vasodilation is deficient in the pulmonary circulation of patients with primary pulmonary hypertension and may contribute to the abnormalities of pulmonary vascular tone and reactivity seen in that condition.
Brett
S J
SJ
Unit of Critical Care, National Heart and Lung Institute, London, UK.
Simon
J
J
Gibbs
R
R
Pepper
J R
JR
Evans
T W
TW
D000241:Adenosine / Q000494:pharmacology*; D002302:Cardiac Output / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects*; D006801:Humans; D006976:Hypertension, Pulmonary / Q000503:physiopathology*; D011667:Pulmonary Veins / Q000187:drug effects / Q000503:physiopathology; D013373:Substance P / Q000494:pharmacology*; D014655:Vascular Resistance / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects*
D013373:Substance P; D000241:Adenosine