Analysis of pulmonary vascular response to acute alveolar hypoxic challenge in young rabbits subjected to chronic hypoxia from birth.
Chronic alveolar hypoxia induces vascular changes leading to pulmonary hypertension. We investigated the role of nitric oxide synthase (NOS) on basal pulmonary artery pressure (PAP) and on changes in PAP arising from an acute alveolar hypoxic challenge (AAHC) in normoxic and chronically hypoxic young rabbits. The chronically hypoxic rabbits were raised from birth in a chamber containing a (10% O2 + 90% N2) gas mixture, whereas the normoxic rabbits were kept in room air. The age of the animals at the time of study (approximately 38 days) was not significantly different between the 2 groups of rabbits. The in vivo PAP was measured using a right heart catheterization technique while the rabbits were spontaneously breathing either a hyperoxic or a hypoxic gas. In the chronically hypoxic group, the AAHC (hypoxic gas) produced a modest increase in PAP. However, after intravenous administration of (100 mg/kg) of the NOS inhibitor, L-NAME (N-nitro-L-arginine methyl ester), a marked increase in PAP was observed when these rabbits were rechallenged with the AAHC. In contrast, in the normoxic rabbits, the AAHC produced only a small increase in PAP, even after pretreatment with L-NAME. In both groups of rabbits, L-NAME led to a significant rise in basal PAP. Using Western blot analysis, we found endothelial NOS (eNOS) protein expression to be significantly increased in pulmonary artery and right ventricular myocardium of the chronically hypoxic rabbits. These results suggest that release of nitric oxide is involved in regulating basal PAP and in modulating the hypoxia-induced pulmonary vasoconstrictor response in immature animals. Moreover, eNOS appears to undergo up-regulation as a consequence of chronic hypoxia.
Baber
Syed R
SR
Department of Pediatrics, Tulane University Health Sciences Center and Tulane University Medical School, New Orleans, Louisiana 70112, USA.
Li
Hong
H
Simakajornboon
Narong
N
Kadowitz
Philip J
PJ
Ross-Ascuitto
Nancy T
NT
Ascuitto
Robert J
RJ
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D015153:Blotting, Western; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006352:Heart Ventricles / Q000187:drug effects / Q000201:enzymology; D006976:Hypertension, Pulmonary / Q000503:physiopathology; D000860:Hypoxia / Q000503:physiopathology*; D008168:Lung / Q000098:blood supply* / Q000378:metabolism / Q000503:physiopathology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III; D011651:Pulmonary Artery / Q000187:drug effects / Q000201:enzymology; D011817:Rabbits; D013997:Time Factors
D004791:Enzyme Inhibitors; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; D019331:NG-Nitroarginine Methyl Ester