Effects of hydralazine on the pulmonary vasculature and respiratory control in humans.
This study sought: (1) to clarify the effects of hydralazine on both the pulmonary vasculature and respiratory control in euoxia and hypoxia in healthy humans; and (2) to determine whether hydralazine alters the expression of genes regulated by hypoxia-inducible factor 1 (HIF-1). Ten volunteers participated in two 2 day protocols. Hydralazine (25 mg) or placebo was administered at 1 pm and 11 pm on the first day, and at 1 pm on the second day. In the mornings and afternoons of both days, we measured plasma vascular endothelial growth factor (VEGF) and erythropoietin (EPO) concentrations (both HIF-1-regulated gene products), systemic arterial blood pressure, and changes in heart rate, cardiac output, maximal systolic pressure difference across the tricuspid valve (delta Pmax) and ventilation in response to 20 min of isocapnic hypoxia. Recent hydralazine: (1) decreased diastolic blood pressure; (2) increased heart rate and cardiac output in euoxia and hypoxia whilst having no effect on delta Pmax; and (3) increased the ventilatory sensitivity to hypoxia. Hydralazine had no effect on plasma EPO or VEGF concentration. We conclude that hydralazine increases the sensitivity of the ventilatory response to hypoxia, but lacks any effect on the pulmonary vasculature at the dose studied. It did not affect the expression of HIF-1-regulated genes.
Liu
Chun
C
Department of Physiology, Anatomy and Genetics, University of Oxford, Sherrington Building, Parks Road, Oxford OX1 3PT, UK.
Balanos
George M
GM
Fatemian
Marzieh
M
Smith
Thomas G
TG
Dorrington
Keith L
KL
Robbins
Peter A
PA
D000328:Adult; D000465:Algorithms; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D004921:Erythropoietin / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006830:Hydralazine / Q000494:pharmacology*; D051793:Hypoxia-Inducible Factor 1 / Q000235:genetics / Q000502:physiology; D008297:Male; D011652:Pulmonary Circulation / Q000187:drug effects*; D015656:Respiratory Mechanics / Q000187:drug effects*; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis / Q000235:genetics; D014665:Vasodilator Agents / Q000494:pharmacology*
D051793:Hypoxia-Inducible Factor 1; D042461:Vascular Endothelial Growth Factor A; D014665:Vasodilator Agents; D004921:Erythropoietin; D006830:Hydralazine