Increased circulating plasma norepinephrine concentrations in noncardiac causes of pulmonary hypertension.

Abstract

Sympathetic nervous system (SNS) activity and circulating norepinephrine (NE) levels may play roles in the elevated pulmonary vascular resistance (PVR) found in patients with pulmonary hypertension. To study the relationship between plasma NE levels, pulmonary NE metabolism, and pulmonary hypertension, we studied 9 patients, suspected of having noncardiac causes of pulmonary hypertension, before and after vasodilator therapy with phentolamine, nitroglycerin, isoproterenol, or hydralazine. Patients were admitted to the ICU and studied using pulmonary artery thermodilution catheters. Seven of 9 patients had noncardiogenic pulmonary hypertension whereas 2 patients did not have hemodynamic evidence of pulmonary hypertension. Simultaneous pulmonary and radial artery samples were analyzed for plasma NE and epinephrine (EPI) content before and after various vasodilator agents. Baseline pulmonary artery (PA) and radial artery NE concentrations correlated (r = .72) with PVR, PA pressures, and PA minus pulmonary capillary wedge (WP) pressures and were increased compared to the 2 patients with normal pulmonary pressures (p less than .01). The normal pulmonary extraction of circulating NE was absent in the 7 patients with pulmonary hypertension. PVR decreased significantly in all 7 patients with each vasodilator (p less than .05); however, the decrease was independent of any change in plasma NE concentration and therapy had no effect on the pulmonary extraction of circulating NE. These data indicate that elevations in plasma NE are coincident with the presence of noncardiogenic pulmonary hypertension and that acute pharmacologic reduction of PVR does not normalize the loss of pulmonary NE metabolism.