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1 Center for Gene Therapy, Columbus Children's Research Institute, Columbus, Ohio, United States; Pediatrics/Neonatology, The Ohio State University, Columbus, Ohio, United States
2 Cell Biology and Physiology, University of New Mexico, School of Medicine, Albuquerque, New Mexico, United States
3 Center for Gene Therapy, Columbus Children's Research Institute, Columbus, Ohio, United States
4 Center For Gene Therapy, Columbus Children's Research Institute, Columbus, Ohio, United States
5 Center for Cardiovascular Medicine, Columbus Children's Research Institute, Columbus, Ohio, United States
6 Center For Perinatal Research, Columbus Children's Research Institute, Columbus, Ohio, United States; Pediatrics/Neonatology, The Ohio State Univerisity, Columbus, Ohio, United States
* To whom correspondence should be addressed. E-mail: chicoinl{at}pediatrics.ohio-state.edu.
Nitric oxide (NO) is an important regulator of vasomotor tone in the pulmonary circulation. We tested the hypothesis that the role NO plays in regulating vascular tone changes during early post-natal development. Isolated, perfused lungs from 7 and 14 day old Sprague-Dawley rats were studied. Baseline total pulmonary vascular resistance (PVR) was not different between age groups. The addition of KCl to the perfusate caused a concentration-dependent increase in PVR, which did not differ between age groups. However, the nitric oxide synthase (NOS) inhibitor N
-nitro-L-arginine augmented the K+-induced increase in PVR in both groups, and the effect was greater in lungs from 14 day old rats vs. 7 day old rats. Lung levels of total eNOS, iNOS and nNOS proteins were not different between groups; however the production rate of exhaled NO was greater in lungs from 14 day olds compared to those of 7 day olds. Vasodilation to 0.1 µM of the NO donor spermineNONOate was greater in 14 day lungs than in 7 day lungs, and lung levels of both soluble guanylyl cyclase and cGMP were greater at 14 days than at 7 days. Vasodilation to 100 µM of the cGMP analogue 8-pCPT-cGMP was greater in 7 day lungs than in 14 day lungs. Our results demonstrate that the pulmonary vascular bed depends more on NO production to modulate vascular tone at 14 days than at 7 days of age. The observed differences in NO sensitivity may be due to maturational increases in soluble guanylyl cyclase protein levels.
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