Forster C
Department of Medicine, University of Toronto, Ontario, Canada.
Eur J Pharmacol. 1995 Sep 5;283(1-3):241-50. doi: 10.1016/0014-2999(95)00364-q.
In this study, the effects of polymyxin B (a protein kinase C inhibitor) on alpha-adrenoceptor stimulation of the canine dorsal pedal artery and saphenous vein were examined. In addition, the question was asked, whether these effects could be altered by the impact of a heart failure state? Blood vessels were obtained at three time points during the development of pacing-induced heart failure in the dog; control (non-paced), 1 week paced and end-stage heart failure. Concentration-effect curves were constructed to the alpha-adrenoceptor agonists, namely, noradrenaline and phenylephrine in the absence and presence of polymyxin B (2 x 10(-5) and 10(-4) M). Responses to noradrenaline and phenylephrine were enhanced in the saphenous vein, but not in the dorsal pedal artery, following the onset of heart failure. In the dorsal pedal artery, polymyxin B was found to inhibit the contractions developed to noradrenaline and phenylephrine to a significant degree (P < 0.05) at control and end-stage heart failure. In contrast, in the saphenous vein, polymyxin B inhibited responses developed to noradrenaline and phenylephrine at all time points studied. This inhibition was always more marked against noradrenaline compared to phenylephrine and, similar to the dorsal pedal artery, became more pronounced at end-stage heart failure. Furthermore, the vein was always more sensitive compared to the artery. Interestingly, as heart failure developed, a non-classical broad concentration-effect curve was evident. The high affinity component was more sensitive to inhibition by polymyxin B. This component was absent at end-stage heart failure in response to phenylephrine.(ABSTRACT TRUNCATED AT 250 WORDS)
在本研究中，检测了多粘菌素B（一种蛋白激酶C抑制剂）对犬足背动脉和大隐静脉α-肾上腺素能受体刺激的影响。此外，还探讨了心力衰竭状态是否会改变这些影响。在犬起搏诱导的心力衰竭发展过程中的三个时间点获取血管；对照组（未起搏）、起搏1周和终末期心力衰竭。在不存在和存在多粘菌素B（2×10⁻⁵和10⁻⁴ M）的情况下，构建了针对α-肾上腺素能受体激动剂去甲肾上腺素和苯肾上腺素的浓度-效应曲线。心力衰竭发生后，大隐静脉对去甲肾上腺素和苯肾上腺素的反应增强，但足背动脉未出现这种情况。在足背动脉中，发现多粘菌素B在对照组和终末期心力衰竭时能显著抑制对去甲肾上腺素和苯肾上腺素产生的收缩（P<0.05）。相比之下，在大隐静脉中，多粘菌素B在所有研究时间点均抑制对去甲肾上腺素和苯肾上腺素的反应。与苯肾上腺素相比，这种抑制对去甲肾上腺素总是更明显，并且与足背动脉相似，在终末期心力衰竭时更为显著。此外，静脉始终比动脉更敏感。有趣的是，随着心力衰竭的发展，出现了一条非经典的宽浓度-效应曲线。高亲和力成分对多粘菌素B的抑制更敏感。在终末期心力衰竭时，对苯肾上腺素的反应中不存在该成分。（摘要截短至250字）
