TY - JOUR
T1 - Developmental effects of endothelin-1 on the pulmonary circulation in sheep
AU - Wong, Jackson
AU - Vanderford, Paula A.
AU - Fineman, Jeffrey R.
AU - Soifer, Scott J.
PY - 1994/9
Y1 - 1994/9
N2 - Endothelin-1 (ET-1) is a polypeptide that has potent hemodynamic effects on the pulmonary circulation. To determine whether there are changes in these effects with increasing postnatal age, we investigated the effects of ET-1 (250 ng/kg) at rest and during pulmonary hypertension in eight lambs (< 1 wk old) and 11 juvenile sheep (6-12 mo old). At rest, ET-1 did not change pulmonary arterial pressure in lambs, but increased pulmonary arterial pressure by 64.0 ± 37.5% (p < 0.05) in sheep. During pulmonary hypertension, ET-1 produced greater decreases in pulmonary arterial pressure in lambs than in sheep (26.6 ± 3.4% versus 18.7 ± 8.3%, p < 0.05). In juvenile sheep, the increase in resting pulmonary arterial pressure produced by ET-1 was inhibited by meclofenamic acid, an inhibitor of prostaglandin synthesis (40.3 ± 9.9% versus 2.3 ± 4.7%, p < 0.05); during pulmonary hypertension, the decrease in pulmonary arterial pressure produced by ET-1 was inhibited by Nω-nitro-L-arginine, an inhibitor of endothelium-derived nitric oxide synthesis (21.4 ± 10.7% versus 8.0 ± 3.6%, p < 0.05) and by glybenclamide, an ATP-dependent potassium-channel blocker (18.8 ± 8.4% versus 4.0 ± 4.4%, p < 0.05). The hemodynamic effects of ET-1 on the pulmonary circulation are dependent on postnatal age. Pulmonary vasoconstriction is mediated by prostaglandin production, and pulmonary vasodilation is mediated, in part, by release of endothelium-derived nitric oxide and activation of ATP-dependent potassium channels.
AB - Endothelin-1 (ET-1) is a polypeptide that has potent hemodynamic effects on the pulmonary circulation. To determine whether there are changes in these effects with increasing postnatal age, we investigated the effects of ET-1 (250 ng/kg) at rest and during pulmonary hypertension in eight lambs (< 1 wk old) and 11 juvenile sheep (6-12 mo old). At rest, ET-1 did not change pulmonary arterial pressure in lambs, but increased pulmonary arterial pressure by 64.0 ± 37.5% (p < 0.05) in sheep. During pulmonary hypertension, ET-1 produced greater decreases in pulmonary arterial pressure in lambs than in sheep (26.6 ± 3.4% versus 18.7 ± 8.3%, p < 0.05). In juvenile sheep, the increase in resting pulmonary arterial pressure produced by ET-1 was inhibited by meclofenamic acid, an inhibitor of prostaglandin synthesis (40.3 ± 9.9% versus 2.3 ± 4.7%, p < 0.05); during pulmonary hypertension, the decrease in pulmonary arterial pressure produced by ET-1 was inhibited by Nω-nitro-L-arginine, an inhibitor of endothelium-derived nitric oxide synthesis (21.4 ± 10.7% versus 8.0 ± 3.6%, p < 0.05) and by glybenclamide, an ATP-dependent potassium-channel blocker (18.8 ± 8.4% versus 4.0 ± 4.4%, p < 0.05). The hemodynamic effects of ET-1 on the pulmonary circulation are dependent on postnatal age. Pulmonary vasoconstriction is mediated by prostaglandin production, and pulmonary vasodilation is mediated, in part, by release of endothelium-derived nitric oxide and activation of ATP-dependent potassium channels.
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U2 - 10.1203/00006450-199409000-00021
DO - 10.1203/00006450-199409000-00021
M3 - Article
C2 - 7808838
AN - SCOPUS:0028059994
SN - 0031-3998
VL - 36
SP - 394
EP - 401
JO - Pediatric Research
JF - Pediatric Research
IS - 3
ER -