Neonatal pulmonary hypertension prevents reorganisation of the pulmonary arterial smooth muscle cytoskeleton after birth.
The pulmonary arterial smooth muscle cell (SMC) cytoskeleton was studied in tissue from 36 piglets aged from within 5 min of birth to 21 d of age, and in 8 adults. An additional 16 piglets were made pulmonary hypertensive by exposure to hypobaric hypoxia (50.8 kPa) for 3 d. In conduit intrapulmonary elastic arteries alpha, beta and gamma actin, the 204, 200 and 196 kDa myosin heavy chain (MHC) isoforms and vinculin were localised by immunohistochemistry. The total actin content, the proportion of monomeric to filamentous alpha and gamma actin and changes in the proportions of the MHC isoforms were determined biochemically. Dividing SMCs were localised and quantified using Ki-67. We found a transient reduction in immunohistochemical expression of gamma actin, 204 kDa MHC isoform and vinculin at 3 and 6 d in the inner media, associated with a transient increase in Ki-67 labelling. The actin content also decreased at 3 and 6 d (P < 0.05), but there was a postnatal, permanent increase in monomeric actin, first the alpha then the gamma isoform. The relative proportions of the MHC isoforms did not change between birth and adulthood in elastic pulmonary arteries but in muscular arteries the 200 kDa isoform increased between 14 d and adulthood. Pulmonary hypertension prevented both the immunohistochemical changes and the postnatal burst of SMC replication and prevented the transient postnatal reduction in actin content. These findings suggest that rapid remodelling of the actin cytoskeleton is an essential prerequisite of a normal postnatal fall in pulmonary vascular resistance.
Hall
S M
SM
Vascular Biology and Pharmacology Unit, Institute of Child Health, London, UK.
Gorenflo
M
M
Reader
J
J
Lawson
D
D
Haworth
S G
SG
D000199:Actins / Q000032:analysis; D000818:Animals; D000831:Animals, Newborn; D003599:Cytoskeleton / Q000737:chemistry / Q000648:ultrastructure*; D004591:Electrophoresis, Polyacrylamide Gel; D006976:Hypertension, Pulmonary / Q000473:pathology*; D015151:Immunoblotting; D007150:Immunohistochemistry / Q000379:methods; D009131:Muscle, Smooth, Vascular / Q000737:chemistry / Q000648:ultrastructure*; D018995:Myosin Heavy Chains / Q000032:analysis; D020033:Protein Isoforms / Q000032:analysis; D013552:Swine; D016596:Vinculin / Q000032:analysis
D000199:Actins; D020033:Protein Isoforms; D016596:Vinculin; D018995:Myosin Heavy Chains