TY - JOUR
T1 - Pulmonary vascular endothelial responses are differentially modulated after cardiopulmonary bypass
AU - Nyhan, Daniel
AU - Gaine, Sean
AU - Hales, Mariesa
AU - Zanaboni, Paul
AU - Simon, Brett A.
AU - Berkowitz, Dan
AU - Flavahan, Nicholas
N1 - Copyright:
Copyright 2007 Elsevier B.V., All rights reserved.
PY - 1999/10
Y1 - 1999/10
N2 - The aim of this study was to characterize the mechanisms underlying pulmonary vascular dysfunction after cardiopulmonary bypass (CPB) by examining responses of isolated pulmonary arteries to selective endothelium- dependent and -independent activators in control and post-CPB dogs. Adult male mongrel dogs were placed on closed-chest, hypothermic CPB for 2.5 h, and then allowed to recover. Anatomically matched pulmonary arterial rings were isolated and suspended for isometric tension recording. Contractile responses to the α1-adrenergic agonist phenylephrine were similar in endothelium- containing arteries from control and CPB animals. Endothelium denudation increased contractions to phenylephrine to a similar extent in both groups. Endothelium-dependent relaxation to acetylcholine was decreased 4 days after CPB compared with controls. In contrast to acetylcholine, endothelium- dependent relaxation to bradykinin or to A23187 were not impaired 4 days after CPB. Inhibition of nitric oxide synthase (NOS) with L-NAME depressed the response to acetylcholine in control vessels, confirming that a component of the response to acetylcholine was nitric oxide (NO) dependent. At lower concentrations of acetylcholine, this component of the response was abolished after CPB. The residual relaxation evoked by acetylcholine in the presence of L-NAME also was impaired in CPB compared with control arteries. This suggests that the CPB-induced impairment of acetylcholine-evoked relaxation may not involve both an NO-mediated and an NO-independent component. L-NAME depressed the response to bradykinin to a similar degree in control and CPB arteries. Vascular smooth-muscle dilatation to the NO donor, SIN-1, or to the K+(ATP)- channel opener, cromakalim, were similar in endothelium-denuded arteries from CPB and control animals. These results suggest that CPB causes a selective impairment in endothelial dilator function without changing the vascular smooth-muscle response to vasodilator or vasoconstrictor stimuli.
AB - The aim of this study was to characterize the mechanisms underlying pulmonary vascular dysfunction after cardiopulmonary bypass (CPB) by examining responses of isolated pulmonary arteries to selective endothelium- dependent and -independent activators in control and post-CPB dogs. Adult male mongrel dogs were placed on closed-chest, hypothermic CPB for 2.5 h, and then allowed to recover. Anatomically matched pulmonary arterial rings were isolated and suspended for isometric tension recording. Contractile responses to the α1-adrenergic agonist phenylephrine were similar in endothelium- containing arteries from control and CPB animals. Endothelium denudation increased contractions to phenylephrine to a similar extent in both groups. Endothelium-dependent relaxation to acetylcholine was decreased 4 days after CPB compared with controls. In contrast to acetylcholine, endothelium- dependent relaxation to bradykinin or to A23187 were not impaired 4 days after CPB. Inhibition of nitric oxide synthase (NOS) with L-NAME depressed the response to acetylcholine in control vessels, confirming that a component of the response to acetylcholine was nitric oxide (NO) dependent. At lower concentrations of acetylcholine, this component of the response was abolished after CPB. The residual relaxation evoked by acetylcholine in the presence of L-NAME also was impaired in CPB compared with control arteries. This suggests that the CPB-induced impairment of acetylcholine-evoked relaxation may not involve both an NO-mediated and an NO-independent component. L-NAME depressed the response to bradykinin to a similar degree in control and CPB arteries. Vascular smooth-muscle dilatation to the NO donor, SIN-1, or to the K+(ATP)- channel opener, cromakalim, were similar in endothelium-denuded arteries from CPB and control animals. These results suggest that CPB causes a selective impairment in endothelial dilator function without changing the vascular smooth-muscle response to vasodilator or vasoconstrictor stimuli.
KW - Acetylcholine
KW - Endothelium-dependent vasodilators
KW - In vitro
KW - Pulmonary circulation
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U2 - 10.1097/00005344-199910000-00007
DO - 10.1097/00005344-199910000-00007
M3 - Article
C2 - 10511126
AN - SCOPUS:0032832866
SN - 0160-2446
VL - 34
SP - 518
EP - 525
JO - Journal of cardiovascular pharmacology
JF - Journal of cardiovascular pharmacology
IS - 4
ER -