SYNTHESIS AND SECRETION OF ATRIAL-NATRIURETIC-FACTOR DURING CHRONIC HYPOXIA - A STUDY IN THE CONSCIOUS INSTRUMENTED RAT

To investigate the mechanisms leading to enhanced synthesis and release of atrial natriuretic factor during chronic hypoxia, we measured immunoreactive plasma atrial natriuretic factor, blood gases, packed cell volume, pulmonary artery pressure and systemic artery pressure in male Sprague-Dawley rats exposed to 1,2 or 3 week of normobaric hypoxia. Rats were implanted with pulmonary and carotid artery catheters and studied conscious, 23 h after return to hypoxia. The concentration of atrial natriuretic factor messenger RNA was measured in the right and left ventricular free walls of rats exposed to 3 weeks of hypoxia and in normoxic control rats. There was a trend for plasma atrial natriuretic factor to increase with the duration of exposure to hypoxia but only the 3-week hypoxic rats had a significantly higher level (1080 ± 193 pg/ml) than the normoxic control rats (318 ± 46 pg/ml, P < 0.05, mean ± SEM). When all the data from normoxic and hypoxic rats were considered together, plasma atrial natriuretic factor was positively correlated wit packed cell volume (r = 0.66, P < 0.001), pulmonary artery pressure (r = 0.68, P < 0.002), and the index of right ventricular hypertrophy (r = 0.54, P < 0.01), but after analysis of partial correlation, packed cell volume was the only independent contributing factor to the variance in the level of plasma atrial natriuretic factor (r2 = 0.24). Three weeks exposure to hypoxia produced a 3.4- and a 2.9-fold increase in atrial natriuretic factor messenger RNA concentration in the right and left ventricles, respectively, suggesting that the increase in pulmonary artery pressure and the resulting right ventricular hyperthrophy may not be the only trigger for the increase in atrial natriuretic factor synthesis and that both ventricles may contribute to the increase in plasma atrial natriuretic factor.