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Published ahead of print on June 7, 2004, doi:10.1164/rccm.200311-1551OC

Am. J. Respir. Crit. Care Med., Volume 170, Number 6, September 2004, 641-646

A more recent version of this article appeared on September 15, 2004
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Submitted on November 17, 2003
Accepted on June 3, 2004

Postnatal Changes in Response to Norepinephrine in the Normal and Pulmonary Hypertensive Lung

Margrid B Schindler1, Alison A Hislop1, and Sheila G Haworth1*

1 Unit of Vascular Biology and Pharmacology, Institute of Child Health, London, United Kingdom

* To whom correspondence should be addressed. E-mail: s.haworth{at}ich.ucl.ac.uk.

The effect of norepinephrine administration on pulmonary blood flow during the neonatal period is unclear. Therfore norepinephrine responses were studied in isolated pulmonary arteries, pulmonary veins and femoral arteries taken from normal pigs from birth to adulthood and from pigs subjected to chronic hypoxia either from birth for 3 days or from 3 to 14 days of age. Normally, the contractile response of pulmonary arteries and veins to norepinephrine decreased after birth (p<0.01) and alpha-2 adrenoceptor mediated relaxation increased in pulmonary arteries and veins and in femoral arteries. Hypoxic exposure from birth prevented the normal postnatal reduction in pulmonary arterial contractile response. Nor was there a postnatal increase in pulmonary arterial adrenoceptor mediated relaxation. When hypoxic exposure followed a period of normal adaptation the pulmonary arterial contractile response was not enhanced but relaxation was significantly impaired. The response of pulmonary veins and femoral arteries was not affected by hypoxic exposure. The contractile effect of norepinephrine was 15-60 fold greater in isolated systemic arteries than in pulmonary arteries taken from both normal and pulmonary hypertensive piglets at all ages. This suggests that use of norepinephrine to manage systemic hypotension in infants and children will not compromise the pulmonary vasculature.
Key words: noradrenaline, adrenoceptors, pulmonary hypertension




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