Atrial natriuretic factor in chronic obstructive lung disease with pulmonary hypertension. Physiological correlates and response to peptide infusion

Abstract

To investigate the physiological role of atrial natriuretic factor (ANF) in patients with hypoxic pulmonary hypertension secondary to chronic obstructive lung disease (COLD), we infused synthetic α-human ANF in seven such patients, and investigated the physiological correlates to circulating peptide levels in 24 patients with COLD. ANF infusion, at incremental rates of 0.01, 0.03, and 0.1 μg/kg · min, increased basal plasma immunoreactive (ir) ANF (136 ± 38 pg/ml) by 3-, 10-, and 26-fold, respectively, and reduced pulmonary artery pressure (from 33 ± 3 to 25 ± 2 mmHg, P < 0.001) and systemic arterial pressure (from 88 ± 4 to 79 ± 4 mmHg, P < 0.001) in a dose-related fashion. Cardiac index increased by 13.5% (P < 0.01) while heart rate was unchanged. Cardiac filling pressures decreased at 0.1 μg/kg · min ANF. Pulmonary and systemic vascular resistance fell by 37% (P < 0.001) and 19% (P < 0.001), respectively. Arterial oxygenation was impaired during ANF infusion, suggesting partial reversal of hypoxic pulmonary vasoconstriction. Plasma renin activity remained unchanged but aldosterone fell by 44% (P < 0.01). The levels of plasma irANF in 24 patients correlated directly with the degree of hemoconcentration (r = 0.67, P < 0.001), respiratory acidosis (r = -0.65, P < 0.001), and pulmonary hypertension (r = 0.52, P < 0.01). The results suggest that ANF may serve as a potent pulmonary vasodilator involved in the circulatory homeostasis of patients with COLD.