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Maturational changes in NO sensitivity are due to increases in soluble gaunylyl cyclase in the developing rat lung
Author(s) -
Chicoine Louis G,
Stenger Michael R,
Metroupolus Matthew J,
Girton Mark R,
Nelin Leif D
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a400-c
Subject(s) - vasodilation , lung , medicine , endocrinology , nitric oxide , vascular resistance , guanylate cyclase , phosphodiesterase , cyclic gmp , respiratory system , chemistry , hemodynamics , enzyme , biochemistry
Nitric oxide (NO) is an important regulator of pulmonary vascular tone in the neonate. We have shown that maturational changes exist in pulmonary NO production during the first weeks of neonatal life. We tested the hypothesis that maturational changes in sensitivity to NO exist in the pulmonary vascular bed. NO has its vasodilatory effect via increased cGMP levels, which depend on the balance between soluble gaunylyl cyclase (sGC) and phosphodiesterase type 5 (PDE‐5) activities. The vasoconstrictor responses to K+ and the subsequent vasodilator responses to 0.1 μM spermineNONOate, a NO donor, were studied in isolated, perfused lungs from 7 and 14 day old Sprague‐Dawley rats in the presence of 300 μM Nù‐nitro‐L‐arginine. 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. The addition of spermineNONOate resulted in greater vasodilation in 14 day lungs than in 7 day lungs. Lungs were harvested from a separate group of age matched animals for determination of cGMP levels, as well as immunoblotting for sGC and PDE‐5. The lung levels of cGMP where greater at 14 days than at 7 days (14.4±2.3 pmol/mL vs. 5.6±0.4 pmol/mL; p≤0.003). Protein levels of sGC were greater at 14 days than at 7 days. There were no differences between 7 day and 14 day lung protein levels of PDE‐5. Our results demonstrate that maturational differences exist in the pulmonary vascular responsiveness to NO, and that these maturational differences in NO sensitivity are due, at least in part, to developmental increases in sGC protein levels.