Pulmonary response of normal human subjects to inhaled vasodilator substances.
1. Inhaled vasodilators such as nitric oxide and epoprostenol (prostaglandin I2) are now widely employed as supportive therapies to improve oxygenation and reduce pulmonary vascular resistance in patients with acute and chronic pulmonary hypertension. However, few data exist concerning their effects in normal individuals. The aim of this study was to characterize the response of the pulmonary circulation in normal individuals to inhaled nitric oxide and nebulized prostaglandin I2.2.Eight healthy volunteers were exposed to inhaled nitric oxide (0, 20 and 40 p.p.m.) and nebulized prostaglandin I2 (10 microgram/ml). Changes in effective pulmonary blood flow and diffusing capacity of the lung for carbon monoxide (TLCO) were measured using respiratory mass spectrometry. Bicycle ergometry was used to increase effective pulmonary blood flow as a positive control.3. Exercise produced significant increases in both effective pulmonary blood flow and TLCO, but neither nitric oxide nor prostaglandin I2 produced significant changes in either parameter.4.No significant change in pulmonary haemodynamics was demonstrated in response to inhaled nitric oxide or nebulized prostaglandin I2, using doses known to be effective in patients with acute and chronic pulmonary hypertension. These data suggest that the normal pulmonary vascular bed is not amenable to vasodilatation by inhaled drugs. The study further suggests that the normal pulmonary vasodilatation seen on exercise is not mediated pharmacologically, but is a secondary consequence to the mechanical effects of a rise in pulmonary blood flow. This study thus supports the view that there is no resting vasoconstrictor tone in the pulmonary vascular bed.
Brett
S J
SJ
Unit of Critical Care, Imperial College School of Medicine, Royal Brompton Hospital, Sydney Street, London SW3 6NP, U.K.
Chambers
J
J
Bush
A
A
Rosenthal
M
M
Evans
T W
TW
D000280:Administration, Inhalation; D000959:Antihypertensive Agents / Q000494:pharmacology; D011464:Epoprostenol / Q000494:pharmacology; D005080:Exercise Test; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D009569:Nitric Oxide / Q000494:pharmacology; D011652:Pulmonary Circulation / Q000187:drug effects*; D011653:Pulmonary Diffusing Capacity / Q000187:drug effects; D018709:Statistics, Nonparametric; D014665:Vasodilator Agents / Q000494:pharmacology*
D000959:Antihypertensive Agents; D014665:Vasodilator Agents; D009569:Nitric Oxide; D011464:Epoprostenol