Pulmonary natriuretic peptide system during rat development.
Maturational changes in the rat lung natriuretic peptide system were studied postnatally in 1-, 4-, and 22-day-old rats. Lung atrial natriuretic factor (ANF) content increased significantly from day 1 to day 4 (712+/-188 vs. 1905+/-520 pg/mg protein; p<0.01) but decreased to 532+/-41 pg/mg protein, on day 22. These changes paralleled ANF messenger RNA (mRNA) detected by reverse transcribed polymerase chain reaction (RT-PCR). Rat pulmonary development also was associated with quantitative and qualitative alterations in ANF receptors. Competitive-binding radioreceptor assays of lung membranes with 125I-ANF and increasing concentrations of unlabeled ANF revealed that the natriuretic peptide receptor-binding sites (Bmax) progressively increased with age from 112 +/-21 fmol/mg protein at day 1 to 211+/-16 (p<0.02) and 326+/-62 fmol/mg protein (p<0.04) in 4- and 22-day-old rats, respectively. Autoradiographic studies of 125I-tyr(0)CNP binding to lung sections revealed that the levels of the natriuretic peptide receptor B (NPR-B) were undetectable. On the other hand, binding of 125I-ANF increased with age, and the higher binding at 4 days was mainly due to increased density of the clearance receptor-C (NPR-C), and at 22 days due to increased natriuretic peptide receptor-A (NPR-A). The increase in natriuretic peptide binding was confirmed at the level of synthesis, where RT-PCR revealed that NPR-A mRNA significantly increased (p<0.01) in 22-day-old rats. In conclusion, these studies demonstrate that the rat pulmonary natriuretic peptide system is altered during development. The altered synthesis of lung natriuretic peptides and their receptors may play a role in the postnatal adaptation of pulmonary circulation.
Jankowski
M
M
Laboratory of Cardiovascular Biochemistry, Centre Hospitalier de L'Universite de Montreal Research Center, Quebec, Canada.
Mukaddam-Daher
S
S
Ernest
S
S
Gutkowska
J
J
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000378:metabolism / Q000502:physiology*; D001667:Binding, Competitive; D007457:Iodine Radioisotopes; D008168:Lung / Q000254:growth & development* / Q000502:physiology*; D010455:Peptides / Q000502:physiology; D011652:Pulmonary Circulation; D012333:RNA, Messenger / Q000378:metabolism / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley
D007457:Iodine Radioisotopes; D010455:Peptides; D012333:RNA, Messenger; D009320:Atrial Natriuretic Factor