The extraction of circulating catecholamines by the lungs in normal man and in patients with pulmonary hypertension.

Abstract

We directly measured the net pulmonary extraction of circulating norepinephrine, epinephrine and dopamine in control patients and patients with primary or secondary pulmonary hypertension. Mixed pulmonary artery norepinephrine, epinephrine and dopamine were 314 +/- 13 pg/ml, 102 +/- 9 pg/ml, 51 +/- 5 pg/ml, respectively, for the control group; values were similar in patients with pulmonary hypertension. The pulmonary extraction of norepinephrine was 25.4 +/- 2.6% (clearance 266 +/- 62 ng/min) in control patients; epinephrine and dopamine were not extracted. There was no net extraction or production of any of the three catecholamines by the lungs in any of the patients with pulmonary hypertension. We conclude that the lungs play a significant role in the inactivation of circulating norepinephrine in man. This metabolic function of the lungs appear to be lost in pulmonary hypertension.

Impairment of Iodine-123-Metaiodobenzylguanidine (¹²³I-MIBG) Uptake in Patients with Pulmonary Artery Hypertension

“…34) During a single pass through the pulmonary circulation, norepinephrine is rapidly extracted and degraded. 35) Sole, et al 36) directly measured the pulmonary extraction of circulating norepinephrine in controls and patients with PH, excluding those with CTEPH. They demonstrated that 25% of circulating norepinephrine is extracted during passage through the normal lung, but the metabolic function of the lung appears to be lost in patients with PH.…”

Changes in arterial norepinephrine concentration following intravenous administration in dogs with lung edema.

“…It is now well established that the lungs of many species can take up and metabolize biogenic amines in vivo and in vitro (Nicholas et al_ 1974; Sole et al 1979 ;Metting et al 1985). Autoradiography (Hughes et al 1969;Nicholas et al 1974) and fluorescence histochemistry (Iwasawa et al 1973) indicated that NE was taken up mainly into endothelial cells, but the mechanisms of the uptake appear to be complicated (Nicholas et al 1974;Metting et al 1985).…”

“…Among them, norepinephrine (NE) is removed up to 30% from the circulation by a single passage of the pulmonary vasculature (Ginn and Vane 1968;Ebel et al 1971 ; Sole et al 1979). The actual site of this process is considered to be at the capillary endothelium (Hughes et al 1969;Fishman and Pietra 1974;Nicholas et al 1974 ;Block and Stalcup 1982).…”

Catecholamine Transport in Isolated Lung Parenchyma of Pig

“…B6nisch, Uhlig & Trendelenburg, 1974) and in kitten isolated coronary arteries (Cornish & Goldie, 1980 (Iwasawa, Gillis & Aghajanian, 1973) and rat lung (Nicholas, Strum, Angelo & Junod, 1974) (Junod & Ody, 1977). It is most unlikely that noradrenergic nerves were involved in the accumulation of any of these catecholamines, since sympathetic innervation of airways smooth muscle is sparse or absent below the level of the bronchi in rat (Zussman, 1966;El-Bermani, 1978), guinea-pig (O'Donnell, Saar & Wood, 1978, rabbit and pig lung (Mann, (Hughes, Gillis & Bloom, 1969;Gillis, 1976) where cocaine and imipramine were potent uptake inhibitors (Iwasawa & Gillis, 1974;Nicholas et al, 1974) (Bakhle & Vane, 1974;Gillis & Roth, 1976;Sole et al, 1979) or in vitro (Gillis, 1976 (Bassett, 1971;Picken & Jarrott, 1975;Brine, Cornish & Miller, 1979). Cocaine (10 uM) and desipramine (1 pM), which did not significantly alter the cellular accumulation of radioactivity from [3H]-Iso, also failed to alter significantly the Iso concentrationeffect curves.…”

“…NA is removed preferentially in perfused rabbit lung, adrenaline (Adr) and Iso being removed at much lower rates (Gillis, 1976). Indeed, in vivo, in man and in animals, neither Adr nor Iso is removed from the pulmonary blood (Bakhle & Vane, 1974; Gillis & Roth, 1976; Sole et al, 1979). However, when catecholamines are administered by inhalation, air-0007-1188/82/080507-07 $01.00 (D The Macmillan Press Ltd 1982 ways rather than vascular smooth muscle is initially exposed to amine.…”