Scarborough N L, Carrier G O
J Pharmacol Exp Ther. 1984 Dec;231(3):603-9.
The mechanism responsible for increased norepinephrine-induced responsiveness of aortas isolated from streptozotocin-diabetic rats compared to age-matched control animals was investigated. Selective alpha-1 and alpha-2 adrenoceptor agonists and antagonists were used to determine the contribution of these receptor subtypes to the norepinephrine-induced contractile response. Findings from these experiments indicated an enhancement of alpha-2 adrenoceptor-mediated contraction in aortas from diabetic rats, whereas alpha-1-mediated responses were not altered. The contribution of extracellular calcium influx to the agonist-induced contractions was determined by using the calcium entry blocker nifedipine. Contractile responses to maximally effective concentrations of norepinephrine, phenylephrine and clonidine were separated into fast and slow components and the effect of increasing concentrations of nifedipine on the responses was determined. These experiments indicated that the fast component of contraction to alpha adrenoceptor agonists was insensitive to nifedipine treatment, whereas the slow component was inhibited effectively. The slow component of contraction in response to norepinephrine and clonidine in aortas from diabetic rats was increased significantly compared to control tissues. These results suggest that there is an increase in alpha-2 adrenoceptor activity in aortas from diabetic rats. Furthermore, the increased aortic contractile responses induced by norepinephrine and selective alpha-2 agonists are due probably to an increased influx of extracellular calcium through nifedipine-sensitive ion channels associated with activation of alpha-2 adrenoceptors.
研究了与年龄匹配的对照动物相比，链脲佐菌素诱导的糖尿病大鼠离体主动脉对去甲肾上腺素反应性增加的机制。使用选择性α-1和α-2肾上腺素能受体激动剂和拮抗剂来确定这些受体亚型对去甲肾上腺素诱导的收缩反应的贡献。这些实验结果表明，糖尿病大鼠主动脉中α-2肾上腺素能受体介导的收缩增强，而α-1介导的反应未改变。通过使用钙通道阻滞剂硝苯地平来确定细胞外钙内流对激动剂诱导的收缩的贡献。将对最大有效浓度的去甲肾上腺素、苯肾上腺素和可乐定的收缩反应分为快速和慢速成分，并确定增加硝苯地平浓度对反应的影响。这些实验表明，对α肾上腺素能受体激动剂的快速收缩成分对硝苯地平治疗不敏感，而慢速成分则受到有效抑制。与对照组织相比，糖尿病大鼠主动脉对去甲肾上腺素和可乐定的收缩反应的慢速成分显著增加。这些结果表明，糖尿病大鼠主动脉中α-2肾上腺素能受体活性增加。此外，去甲肾上腺素和选择性α-2激动剂诱导的主动脉收缩反应增加可能是由于细胞外钙通过与α-2肾上腺素能受体激活相关的硝苯地平敏感离子通道内流增加所致。
