Kamata K, Miyata N, Kasuya Y
Department of Pharmacology, School of Pharmacy, Hoshi University, Tokyo, Japan.
J Pharmacobiodyn. 1988 Oct;11(10):707-13. doi: 10.1248/bpb1978.11.707.
To investigate the influence of diabetes on the responsiveness of the cardiovascular system, we have examined the effects of various agents on the reactivity of the vascular smooth muscle of aortic strips obtained from age-matched control and diabetic rats. Norepinephrine (NE) contracted the aortic strips obtained from age-matched control and diabetic rats in a concentration-dependent manner, but maximal contraction of aortic strips in response to NE was enhanced in diabetic rats. The EC50 value for NE in the diabetic aortic strips was similar to that in the aorta from age-matched controls. Ca-induced contracture of the aortic strips which were depolarized with isotonic K+ (60 mM) was potentiated in aortic strips from diabetic rats, when compared with those from age-matched controls. Ca-induced contracture of aortic strips, preincubated with 10(-6) M NE and 10(-6) M nicardipine in Ca2+-free Krebs-Henseleit solution (KHS), was not significantly different in age-matched control and diabetic rats. Bay K 8644, an activator of calcium channels, produced an increase in the force of contraction of the slightly depolarized aorta from diabetic rats. Phasic contraction induced by phenylephrine (PE) in the presence of 10(-6) M nicardipine in Ca2+-free KHS was significantly enhanced in aortic strips obtained from diabetic rats. These results demonstrate that NE-induced contraction of the aortic strips obtained from diabetic rats was significantly enhanced, and that this increased contractile response of the aorta to NE may be due to an increased influx of extracellular calcium through the voltage-dependent Ca2+ channels, but not through the receptor-operated Ca2+ channels.(ABSTRACT TRUNCATED AT 250 WORDS)
为研究糖尿病对心血管系统反应性的影响，我们检测了多种药物对从年龄匹配的对照大鼠和糖尿病大鼠获取的主动脉条血管平滑肌反应性的作用。去甲肾上腺素（NE）以浓度依赖方式使年龄匹配的对照大鼠和糖尿病大鼠的主动脉条收缩，但糖尿病大鼠主动脉条对NE的最大收缩反应增强。糖尿病主动脉条中NE的半数有效浓度（EC50）值与年龄匹配对照大鼠主动脉中的相似。与年龄匹配的对照大鼠相比，用等渗钾离子（60 mM）去极化的糖尿病大鼠主动脉条的钙诱导挛缩增强。在无钙的克氏-亨氏液（KHS）中用10⁻⁶ M NE和10⁻⁶ M尼卡地平预孵育的主动脉条的钙诱导挛缩，在年龄匹配的对照大鼠和糖尿病大鼠中无显著差异。钙通道激活剂Bay K 8644使糖尿病大鼠轻度去极化的主动脉收缩力增加。在无钙KHS中10⁻⁶ M尼卡地平存在下，苯肾上腺素（PE）诱导的阶段性收缩在糖尿病大鼠主动脉条中显著增强。这些结果表明，糖尿病大鼠主动脉条对NE诱导的收缩显著增强，且主动脉对NE这种增加的收缩反应可能是由于细胞外钙通过电压依赖性钙通道的内流增加，而非通过受体操纵性钙通道。（摘要截短于250词）
