title: Three-week neonatal hypoxia reduces blood CGRP and causes persistent pulmonary hypertension in rats.
abstract: To increase understanding of persistent pulmonary hypertension, we examined chronic pulmonary effects of hypoxia at birth and their relationships with immunoreactive levels of the potent vasodilator, calcitonin gene-related peptide (CGRP). Rats were born in 10% hypobaric hypoxia, where they remained for 1-2 days, or in 15% hypoxia, where they remained for 21 days. All were then reared in normoxia for 3 mo followed by reexposure to 10% hypoxia for 7 days (H-->H) or continued normoxia (H-->N); age-matched normoxic rats were hypoxic for the last 7 days (N-->H) or normoxic throughout (N-->N). Results are as follows. Pulmonary arterial pressure (P(PA)) in 10% H-->N rats was normal at the end of the experiment (13 wk), but in rats reexposed to hypoxia (H-->H), pressure rose to 19% above N-->H controls. In 15% H-->N rats, P(PA) remained high, similar to that of N-->H rats, and increased further by 40% on reexposure (H-->H). Medial thickness of small pulmonary arteries in 10% H-->H rats also increased by 40% over N-->H controls and was equally high in 15% H-->N and H-->H rats. In N-->H rats from both experiments, right ventricular hypertrophy index (RVH) was increased after hypoxia at 15-16 wk. Also, in the 15% study, RVH remained elevated in H-->N rats and increased in H-->H rats by 19% above N-->H controls. Blood CGRP was reduced by neonate and adult hypoxia, and hypoxic reexposure (H-->H) further lowered blood CGRP in the 15% but not 10% study. Declining left ventricular blood CGRP correlated highly with logarithmically increasing P(PA) in the 15% study (r = -0.81, P = 0.000). In conclusion, 1) short perinatal exposure to 10% O(2) exacerbated pulmonary hypertension with hypoxia later in life, 2) 15% O(2) at birth and for 21 days caused persistent pulmonary hypertension and exacerbation with reexposure, and 3) P(PA) correlated highly with declining blood CGRP levels in the 15% study.
authors.affiliation: Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin, Madison, Wisconsin 53706, USA. keithi@svm.vetmed.wisc.edu
authors.forename: I M
authors.initials: IM
authors.lastname: Keith
authors.forename: S
authors.initials: S
authors.lastname: Tjen-A-Looi
authors.forename: H
authors.initials: H
authors.lastname: Kraiczi
authors.forename: R
authors.initials: R
authors.lastname: Ekman
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001794:Blood Pressure; D015740:Calcitonin Gene-Related Peptide / Q000097:blood* / Q000378:metabolism; D006400:Hematocrit; D006976:Hypertension, Pulmonary / Q000209:etiology* / Q000503:physiopathology; D017380:Hypertrophy, Right Ventricular / Q000209:etiology / Q000473:pathology; D000860:Hypoxia / Q000097:blood* / Q000150:complications* / Q000503:physiopathology; D008168:Lung / Q000378:metabolism; D009206:Myocardium / Q000473:pathology; D009929:Organ Size; D011651:Pulmonary Artery / Q000473:pathology / Q000503:physiopathology; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values
chemical_list: D015740:Calcitonin Gene-Related Peptide