Received July 27, 2007
Revised August 31, 2007
Accepted after revision September 19, 2007

¹ University of Oxford
² University of Birmingham

^* To whom correspondence should be addressed. E-mail: peter.robbins{at}physiol.ox.ac.uk.

	Abstract

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-regulated gene products), systemic arterial blood pressure, and changes in heart rate, cardiac output, maximum systolic pressure difference across the tricuspid valve (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 Pmax; 3) increased the ventilatory sensitivity to hypoxia. Hydralazine had no effect on plasma EPO and VEGF concentration. We conclude that hydralazine increases the sensitivity of the ventilatory response to hypoxia, but lacks any effect at the dose studied on the pulmonary vasculature. It did not affect the expression of HIF-regulated genes.

Key Words: Hypoxia, Pulmonary circulation, Respiratory control