Circulating and urinary levels of endothelin (ET), an endothelium-derived vasoconstrictive and mitogenic peptide have been reported to increase in patients with chronic obstructive pulmonary disease (COPD), but the mechanisms of these abnormalities are not fully understood. Our study objectives were to evaluate pulmonary and renal ET clearance in COPD patients during an acute exacerbation. Our participants included nine consecutive patients with moderate to severe COPD without signs of right heart failure admitted for acute exacerbation and ten healthy volunteers (HV) as controls. ET was detected by radioimmunoassay in venous and arterial blood as well as in a timed urine specimen. For each subject, arterial/venous immunoreactive ET ratio (ir-ETart/ir-ETven) was evaluated as an index of its pulmonary clearance. Creatinine clearance was employed in each case to obtain a corrected renal ir-ET clearance. Glomerular filtration rate (GFR) was also assessed by dynamic99mTc-diethylenetriamine pentaacetic acid renal scintigraphy in six COPD patients during acute exacerbation and at recovery. The ratio ir-ETart/ir-ETven was comparable in COPD patients (0.75±0.12) and in HV (0.82±0.09). A significant difference was found with respect to 24 h ir-ET urinary excretion between COPD patients during exacerbation as well as at recovery (respectively 142.1±12.8 ng/24 h and 89.0±15.1 ng/24 h) and HV (65.1±10.1 ng/24 h). ET renal clearance was higher in COPD patients than in HV (29.2±5.2 ml min−1in COPD during exacerbation; 17.5±3.9 ml min−1at recovery and 13.6±2.4 ml min−1in HV, P<0.001). GFR was 69.4±10.0 ml min−1in COPD patients during exacerbation and it significantly increased at the recovery (95.5±20.9 ml min−1P<0.001). Corrected renal clearance of the peptide was significantly correlated to GFR values during the exacerbation (r=−0.81, P<0.05). Furthermore change in renal ET production resulted associated with changes in paCO2(r=0.83, P<0.001) and in paO2(r=−0.73 , P<0.05). Acute exacerbation in COPD patients causes an increase in renal ET production which is partially reversible at the recovery, in the absence of significant changes in ET-1 circulating levels. ET might contribute to the renal response to hypoxaemia and hypercapnia in COPD.

Abnormalities of renal endothelin during acute exacerbation in chronic obstructive pulmonary disease / Sofia, Matteo; Maniscalco, M.; Celentano, Luigi; Faraone, S.; Mormile, Mauro; Alifano, M.; Carratù, L.. - In: PULMONARY PHARMACOLOGY & THERAPEUTICS. - ISSN 1094-5539. - STAMPA. - 14:4(2001), pp. 321-327. [10.1006/pupt.2001.0303]

Abnormalities of renal endothelin during acute exacerbation in chronic obstructive pulmonary disease.

SOFIA, MATTEO;M. Maniscalco;CELENTANO, LUIGI;MORMILE, MAURO;
2001

Abstract

Circulating and urinary levels of endothelin (ET), an endothelium-derived vasoconstrictive and mitogenic peptide have been reported to increase in patients with chronic obstructive pulmonary disease (COPD), but the mechanisms of these abnormalities are not fully understood. Our study objectives were to evaluate pulmonary and renal ET clearance in COPD patients during an acute exacerbation. Our participants included nine consecutive patients with moderate to severe COPD without signs of right heart failure admitted for acute exacerbation and ten healthy volunteers (HV) as controls. ET was detected by radioimmunoassay in venous and arterial blood as well as in a timed urine specimen. For each subject, arterial/venous immunoreactive ET ratio (ir-ETart/ir-ETven) was evaluated as an index of its pulmonary clearance. Creatinine clearance was employed in each case to obtain a corrected renal ir-ET clearance. Glomerular filtration rate (GFR) was also assessed by dynamic99mTc-diethylenetriamine pentaacetic acid renal scintigraphy in six COPD patients during acute exacerbation and at recovery. The ratio ir-ETart/ir-ETven was comparable in COPD patients (0.75±0.12) and in HV (0.82±0.09). A significant difference was found with respect to 24 h ir-ET urinary excretion between COPD patients during exacerbation as well as at recovery (respectively 142.1±12.8 ng/24 h and 89.0±15.1 ng/24 h) and HV (65.1±10.1 ng/24 h). ET renal clearance was higher in COPD patients than in HV (29.2±5.2 ml min−1in COPD during exacerbation; 17.5±3.9 ml min−1at recovery and 13.6±2.4 ml min−1in HV, P<0.001). GFR was 69.4±10.0 ml min−1in COPD patients during exacerbation and it significantly increased at the recovery (95.5±20.9 ml min−1P<0.001). Corrected renal clearance of the peptide was significantly correlated to GFR values during the exacerbation (r=−0.81, P<0.05). Furthermore change in renal ET production resulted associated with changes in paCO2(r=0.83, P<0.001) and in paO2(r=−0.73 , P<0.05). Acute exacerbation in COPD patients causes an increase in renal ET production which is partially reversible at the recovery, in the absence of significant changes in ET-1 circulating levels. ET might contribute to the renal response to hypoxaemia and hypercapnia in COPD.
2001
Abnormalities of renal endothelin during acute exacerbation in chronic obstructive pulmonary disease / Sofia, Matteo; Maniscalco, M.; Celentano, Luigi; Faraone, S.; Mormile, Mauro; Alifano, M.; Carratù, L.. - In: PULMONARY PHARMACOLOGY & THERAPEUTICS. - ISSN 1094-5539. - STAMPA. - 14:4(2001), pp. 321-327. [10.1006/pupt.2001.0303]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/343388
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