O'Murchu B, Miller V M, Perrella M A, Burnett J C
Department of Surgery, Mayo Clinic and Foundation, Rochester, Minnesota 55905.
J Clin Invest. 1994 Jan;93(1):165-71. doi: 10.1172/JCI116940.
Experiments were designed to determine whether a heterogeneity of endothelium-dependent relaxations in arteries from different vascular beds exists in experimental congestive heart failure (CHF) and to determine the mediators of those responses. CHF was produced in dogs by rapid ventricular pacing for 15 d. Rings of coronary, femoral, and renal arteries with and without endothelium from control and CHF dogs were suspended in organ chambers for measurement of isometric force. In arteries contracted with prostaglandin F2 alpha, endothelium-dependent relaxations to BHT 920 (an alpha 2-adrenergic agonist) were increased in coronary arteries from dogs with CHF (maximal relaxation: control -15 +/- 9% vs CHF -92 +/- 5%; n = 5-6; P < 0.05), with a modest enhancement in renal arteries. Relaxations to adenosine diphosphate and the calcium ionophore were unchanged. Relaxations to BHT 920 in CHF were reduced by NG monomethyl-L-arginine (L-NMMA) and pertussis toxin but not by indomethacin. These data suggest that endothelium-dependent relaxations are affected heterogeneously in CHF. The enhanced response to alpha 2-adrenergic agonists in the coronary artery is mediated by nitric oxide through a mechanism sensitive to inhibition by pertussis toxin. This selective increase in endothelium-dependent relaxations in the coronary artery may contribute to preserving coronary blood flow during CHF.
实验旨在确定在实验性充血性心力衰竭（CHF）中，不同血管床动脉的内皮依赖性舒张是否存在异质性，并确定这些反应的介质。通过快速心室起搏15天在犬身上制造CHF。将来自对照犬和CHF犬的有或无内皮的冠状动脉、股动脉和肾动脉环悬挂在器官浴槽中以测量等长力。在用前列腺素F2α收缩的动脉中，CHF犬冠状动脉对BHT 920（一种α2肾上腺素能激动剂）的内皮依赖性舒张增强（最大舒张：对照-15±9% vs CHF-92±5%；n = 5-6；P < 0.05），肾动脉有适度增强。对二磷酸腺苷和钙离子载体的舒张无变化。CHF中对BHT 920的舒张被NG-单甲基-L-精氨酸（L-NMMA）和百日咳毒素降低，但不被吲哚美辛降低。这些数据表明CHF中内皮依赖性舒张受到异质性影响。冠状动脉中对α2肾上腺素能激动剂的增强反应由一氧化氮通过对百日咳毒素抑制敏感的机制介导。冠状动脉中内皮依赖性舒张的这种选择性增加可能有助于在CHF期间维持冠状动脉血流。
