Depressed beta-adrenergic receptor- and endothelium-mediated vasodilation in conscious dogs with heart failure.
Depressed beta-adrenergic receptor- and endothelium-mediated vasodilation in conscious dogs with heart failure.
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患有心力衰竭的清醒犬体内β-肾上腺素能受体和内皮介导的血管舒张受到抑制。
DOI：
10.1161/01.res.73.6.1013
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发表时间：
1993
影响因子：
20.1
通讯作者：
Vatner,SF
中科院分区：
文献类型：
--
作者：
Kiuchi,K;Sato,N;Shannon,RP;Vatner,DE;Morgan,K;Vatner,SF
在11只清醒的狗中，在起搏诱导的心力衰竭（HF）中检查外周血管舒张反应性，该狗长期用于测量全身（总外周阻力[TPR]）和局部（髂血流）血管阻力。在起搏前（对照）和快速心室起搏4 - 7周后，在同一只狗中检查了对异丙肾上腺素（ISO）、乙酰胆碱（ACh）和硝酸甘油（NTG）的剂量反应，以左心室舒张末期压升高为特征（6.7 +/- 0.4 [对照] vs 28 +/- 1.5 [HF] mm Hg）和心输出量（-30 +/- 5%）和左心室dP/dt（-53 +/- 3%）降低，以及腹水和外周水肿。在对照状态下，ISO（100 ng/kg）使TPR下降57 +/- 2%，ACh（3微克/kg）使TPR下降61 +/- 3%，NTG（10微克/kg）使TPR下降55 +/- 2%。在HF中，在相同剂量的ISO（-50 +/-2%）和ACh（-49 +/-2%）下观察到TPR的较小降低（P <0.05），但在NTG（-58 +/-3%）下没有观察到TPR的较小降低。抑郁反应全身ISO和乙酰胆碱，但不是NTG，观察HF中存在的神经节阻滞，也在局部给药后的小剂量的药物在没有神经节阻滞，但全身效应没有引起。一氧化氮合酶抑制剂在HF前（+154 +/- 28% [对照]）比HF后（+80 +/- 22% [HF]）更大程度地增加TPR，消除了对ACh的抑制反应，但对ISO的抑制反应没有消除。通过125 I-氰基吲哚酚结合肠系膜血管膜制备物测定的β-肾上腺素能受体密度在HF后显著降低（130 +/- 3 [对照]对100 +/- 8 [HF] fmol/mg，P <0.05），亲和力无任何变化。因此，外周血管β-肾上腺素能受体下调发生在HF，独立于改变内皮介导的外周血管舒张。
Peripheral vasodilator responsiveness was examined in pacing-induced heart failure (HF) in 11 conscious dogs chronically instrumented for measurement of systemic (total peripheral resistance [TPR]) and local (iliac blood flow) vascular resistance. Dose responses to isoproterenol (ISO), acetylcholine (ACh), and nitroglycerin (NTG) were examined in the same dogs before pacing (control) and after 4 to 7 weeks of rapid ventricular pacing, which induced congestive HF, characterized by increased left ventricular end-diastolic pressure (6.7 +/- 0.4 [control] versus 28 +/- 1.5 [HF] mm Hg) and decreased cardiac output (-30 +/- 5%) and left ventricular dP/dt (-53 +/- 3%), as well as ascites and peripheral edema. In the control state, TPR fell by 57 +/- 2% in response to ISO (100 ng/kg), by 61 +/- 3% in response to ACh (3 micrograms/kg), and by 55 +/- 2% in response to NTG (10 micrograms/kg). In HF, smaller decreases (P < .05) in TPR were observed with the same doses of ISO (-50 +/- 2%) and ACh (-49 +/- 2%) but not with NTG (-58 +/- 3%). Depressed responses to systemic ISO and ACh, but not NTG, were observed in HF in the presence of ganglionic blockade and also after local administration of smaller doses of the drugs in the absence of ganglionic blockade, but where systemic effects were not elicited. Inhibition of nitric oxide synthase increased TPR to a greater degree before HF (+154 +/- 28% [control]) than after (+80 +/- 22% [HF]) and eliminated the depressed responses to ACh but not to ISO. beta-Adrenergic receptor density, as determined by 125I-cyanopindolol binding in membrane preparations from mesenteric vessels was significantly decreased after HF (130 +/- 3 [control] versus 100 +/- 8 [HF] fmol/mg, P < .05) without any change in affinity. Thus, peripheral vascular beta-adrenergic receptor downregulation occurs in HF, independent of altered endothelium-mediated peripheral vasodilation.