Response of the pulmonary circulation to acetylcholine, calcitonin gene-related peptide, substance P and oral nicardipine in patients with primary pulmonary hypertension.
Endothelium-dependent vasodilation of the pulmonary vascular bed was investigated in five patients with primary pulmonary hypertension. Three endothelium-dependent vasodilators (acetylcholine, calcitonin gene-related peptide and substance P [in two patients]) were infused sequentially into the right atrium, followed by nicardipine given orally during full hemodynamic monitoring. Acetylcholine, calcitonin gene-related peptide and substance P had no effect on pulmonary artery pressure, total pulmonary vascular resistance or cardiac output, although calcitonin gene-related peptide significantly decreased systemic arterial systolic pressure from 132 +/- 34 to 113 +/- 33 mm Hg. In contrast, oral nicardipine decreased total pulmonary vascular resistance from 23 +/- 12 to 13 +/- 8 U, with a concomitant increase in cardiac output from 3.1 +/- 1 to 4.7 +/- 2 liters.min-1 and decrease in systemic vascular resistance from 30 +/- 9 to 13 +/- 4 U. Thus, despite the presence of a reversible component in these five patients with primary pulmonary hypertension, pulmonary vascular resistance did not decrease in response to the infused endothelium-dependent vasodilator agents, indicating that endothelium-dependent vasodilation is impaired in these patients.
Department of Medicine, Hammersmith Hospital, London, England.
N G
NG
Uren
P F
PF
Ludman
T
T
Crake
C M
CM
Oakley
D000109:Acetylcholine / Q000494:pharmacology*; D000328:Adult; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology*; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000503:physiopathology*; D008297:Male; D009529:Nicardipine / Q000494:pharmacology*; D011651:Pulmonary Artery / Q000187:drug effects / Q000503:physiopathology*; D011652:Pulmonary Circulation / Q000502:physiology; D013373:Substance P / Q000494:pharmacology*; D014655:Vascular Resistance / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects*
D013373:Substance P; D009529:Nicardipine; D015740:Calcitonin Gene-Related Peptide; D000109:Acetylcholine