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1Department of Pharmacology, Institute of Pharmacology and Toxicology, School of Medicine, Universidad Complutense and 3Instituto de Cardiología, Hospital Universitario San Carlos, Madrid, Spain; and 2Department of Pediatrics, University Hospital Maastricht, Research Institute Growth and Development, Maastricht, The Netherlands
Submitted 29 June 2004 ; accepted in final form 15 September 2004
The nitric oxide (NO)/cGMP pathway plays a key role in the regulation of pulmonary vascular tone during the transition from the fetal to the neonatal circulation, and it is impaired in pathophysiological conditions such as pulmonary hypertension. In the present study, we have analyzed the changes in the function and expression of soluble guanylyl cyclase (sGC) in pulmonary arteries during early postnatal maturation in isolated third-branch pulmonary arteries from newborn (318 h of age) and 2-wk-old piglets. The expression of sGC
1-subunit in pulmonary arteries increased with postnatal age both at the level of mRNA and protein. The catalytic region of porcine sGC
1 was sequenced, showing a 92% homology with the human sequence. This age-dependent increase in sGC expression correlated with increased vasorelaxant responses to the physiological sGC activator NO and to the exogenous sGC activator YC-1, but not to the membrane-permeable cGMP analog 8-bromoguanosine 3',5'-cyclic monophosphate. In conclusion, an increased expression of sGC in pulmonary conduit arteries from 2-wk-old compared with newborn piglets explains, at least partly, the age-dependent increase in the vasorelaxant response of NO and other activators of sGC.
newborn; YC-1; vascular smooth muscle
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