PULMONARY VASCULAR RESPONSIVENESS IN RATS FOLLOWING NEONATAL EXPOSURETO HIGH-ALTITUDE OR CARBON-MONOXIDE

Exposure of adult and neonatal rats to high altitude increases pulmona ry vascular responsiveness during the exposure. A study was undertaken to determine if a short exposure of neonatal rats to either high-alti tude or carbon monoxide (CO) hypoxia would cause persistent alteration s in pulmonary vascular responsiveness postexposure. One-day-old male Sprague-Dawley rats were obtained as 16 litters of 10-12 pups each. At 2 days of age, 4 litters were exposed to CO (500 ppm) for 32 days, an d 4 litters were exposed to ambient air (AIR) in Detroit (200 m). Anot her 4 litters were exposed to 3500 m altitude (ALT) in a chamber for 3 2 days, and 3 litters were exposed to ambient conditions in Fort Colli ns (CON, 1524 m). After the exposures, all rats were maintained at 152 4 m. At 2, 40, 76, and 112 days postexposure, lungs were isolated and perfused with Earle's salt solution (+Ficoll, 4 g%). Pulmonary vascula r responsiveness was assessed by dose responses to angiotensin II (AII , 0.025-0.40 mug) and acute hypoxia (3% O2 for 3 min). AII responses w ere higher in ALT vs CON rats at all ages, but no differences were not ed between CO and AIR rats. Acute hypoxic responses were higher in ALT versus CON rats at 2 and 40 days postexposure, but no differences wer e noted between CO and AIR rats. Baseline pulmonary vascular resistanc e and pulmonary arterial pressure (in isolated lungs) were higher in A LT rats at all four ages compared to the other three groups. Both the ALT and CO rats displayed hypertrophy of the right ventricle (RV) and the left ventricle (LV) at the termination of treatment and elevated h ematocrit. LV hypertrophy and polycythemia regressed with time, but RV hypertrophy remained significant in the ALT rats through 112 days pos texposure. The results indicate that neonatal exposure to ALT, but not CO, causes a persistent increase in pulmonary vascular responsiveness and RV hypertrophy for at least 112 days after termination of the exp osure.