The role of angiotensin II receptor-1 blockade in the hypoxic pulmonary vasoconstriction response in newborn piglets.
BACKGROUND
Angiotensin-converting enzyme activity is increased in newborn infants with respiratory distress syndrome and in animals with alveolar hypoxia.


OBJECTIVE
To test whether angiotensin II (Ang II) mediates the pulmonary vasoconstriction induced by acute hypoxia in newborn piglets.


METHODS
Eight unanesthetized chronically instrumented newborn piglets (mean +/- SEM; age 6.6 +/- 0.6 days; weight 2,181 +/- 174 g) were randomly assigned to receive a saline solution or the Ang II type 1 receptor (AT(1)) antagonist, losartan, in a crossover study design, with an interval of at least 48 h between the first and second study. Pulmonary artery (Ppa), wedge, systemic arterial (Psa) and right atrial pressures, cardiac output (CO), pulmonary (PVR) and systemic (SVR) vascular resistances, and arterial blood gases were obtained in room air, before and during the saline or losartan infusion (6 mg/kg followed by 3 mg/kg/h), and during 6 h of hypoxia (FiO(2) = 0.11) and saline or losartan infusion. Data were analyzed by repeated measures analysis of variance.


RESULTS
The pulmonary vasoconstriction induced by acute hypoxia was significantly attenuated during losartan infusion, while Psa, SVR, CO, pH, PaCO(2), PaO(2) and base excess did not differ between groups. During room air, Ppa, PVR, Psa, SVR and CO values were not modified by saline or losartan infusion.


CONCLUSIONS
These data suggest that the pulmonary vasoconstriction induced by acute hypoxia in newborn piglets is partially mediated by Ang II, acting via AT(1).
Division of Neonatology, Department of Pediatrics, University of Miami Miller School of Medicine, Miami, Fla. 33101, USA.
José Simon
JS
Camelo
Dorothy
D
Hehre
Carlos
C
Devia
Sílvia Helena Henriques
SH
Camelo
Eduardo
E
Bancalari
Cleide
C
Suguihara
D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D000831:Animals, Newborn; D002302:Cardiac Output; D003251:Constriction, Pathologic; D004195:Disease Models, Animal; D006439:Hemodynamics / Q000187:drug effects; D000860:Hypoxia / Q000503:physiopathology*; D019808:Losartan / Q000494:pharmacology*; D011651:Pulmonary Artery / Q000503:physiopathology*; D044140:Receptor, Angiotensin, Type 1 / Q000502:physiology*; D013552:Swine
D047228:Angiotensin II Type 1 Receptor Blockers; D057911:Angiotensin Receptor Antagonists; D044140:Receptor, Angiotensin, Type 1; D019808:Losartan