Role of Angiotensin II Receptor Blockade on Hypoxic Pulmonary Hypertension in Newborn Piglets

Abstract 1749 Poster Session I, Saturday, 5/1 (poster 106)

Angiotensin-converting enzyme activity is increased in newborn infants with respiratory distress syndrome and chronic alveolar hypoxia. Chronic hypoxic pulmonary hypertension is attenuated by angiotensin II receptor 1 (AT₁) blockade in adult animals. To test whether angiotensin II (AT) is one of the mediators in the acute hypoxic pulmonary hypertension in newborn animals, 8 unanesthetized chronically instrumented piglets (mean ± SD; age, 6.5 ± 1.8 days; weight, 2181 ± 493 g) were randomly assigned to receive saline as a placebo solution (P) or AT₁ antagonist, Losartan (L), in a crossover study design, with at least 48 hours interval between the first and the second study. Pulmonary artery (Pap), wedge (Pwp), systemic arterial (Psa) and right atrial (Rap) pressures, cardiac output (CO), pulmonary (PVR) and systemic (SVR) vascular resistances, and arterial blood gases were obtained in normoxia, before and during P or L infusion (6 mg/kg as a bolus, followed by 3 mg/kg/h), and during 6 hours of hypoxia (FiO₂ = 0.11). Cardiac output was measured by thermodilution technique. Data were analyzed by repeated measures analysis of variance. Results (mean ± SD) are as follows: (Table)

Table 1 No caption available

The acute hypoxic pulmonary hypertension was significantly attenuated during L infusion, while Psa, SVR, CO, pH, PaCO₂, PaO₂ and BE did not differ between the groups. During normoxia, Pap, Pwp, PVR, Psa, SVR and CO values were not modified by P or L infusion. These data demonstrate that the acute hypoxic pulmonary hypertension is in part mediated by an increase in endogenous levels of angiotensin II in newborn piglets.