Three-week neonatal hypoxia reduces blood CGRP and causes persistent pulmonary hypertension in rats.
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.
Keith
I M
IM
Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin, Madison, Wisconsin 53706, USA. keithi@svm.vetmed.wisc.edu
Tjen-A-Looi
S
S
Kraiczi
H
H
Ekman
R
R
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
D015740:Calcitonin Gene-Related Peptide