Nakasone J, Higuchi M, Miyagi K, Matsuzaki T, Noguchi K, Sakanashi M, Yamashiro S, Itomine T, Sakanashi M
Department of Pharmacology, School of Medicine, University of the Ryukyus, Okinawa, Japan.
Arzneimittelforschung. 2000 Dec;50(12):1078-83. doi: 10.1055/s-0031-1300344.
The influence of extracellular Ca2+ concentration on contractile responses of aortae isolated from diabetic rats to KCl and alpha-adrenoceptor agonists was compared with that of non-diabetic rat aortae. Diabetic rats 6 weeks after administration of streptozotocin showed significantly lower body weight and higher plasma glucose concentration, but the protein content per each aortic ring preparation was not significantly different from that of non-diabetic preparation. Both diabetic and non-diabetic aortae showed concentration-dependent contractile responses to norepinephrine, which were concentration-dependently inhibited by prazosin. On the other hand, clonidine induced small contractions in both aortae, which tended to be more inhibited by prazosin than yohimbine. In non-diabetic aortae, the contractile responses to KCl, norepinephrine, methoxamine and clonidine were significantly greater with 2.5 mmol/l of extracellular Ca2+ than 1.25 mmol/l. In diabetic aortae, however, the contractile responses were not significantly influenced by changes in extracellular Ca2+ concentration. Additionally, the contractile responses to each agonist were markedly greater in non-diabetic aortae than diabetic ones. The present results indicate that the contractions of diabetic vasculature do not respond to changes in extracellular Ca2+ concentration, suggesting that there may be some impairment of Ca2+ related mechanisms.
将链脲佐菌素给药6周后的糖尿病大鼠主动脉对氯化钾和α-肾上腺素能激动剂的收缩反应中细胞外钙离子浓度的影响,与非糖尿病大鼠主动脉的进行了比较。链脲佐菌素给药6周后的糖尿病大鼠体重显著降低,血糖浓度升高,但每个主动脉环标本的蛋白质含量与非糖尿病标本相比无显著差异。糖尿病和非糖尿病主动脉对去甲肾上腺素均表现出浓度依赖性收缩反应,且这些反应被哌唑嗪浓度依赖性抑制。另一方面,可乐定在两种主动脉中均引起小幅度收缩,哌唑嗪对其抑制作用往往比对育亨宾的抑制作用更强。在非糖尿病主动脉中,细胞外钙离子浓度为2.5 mmol/L时对氯化钾、去甲肾上腺素、甲氧明和可乐定的收缩反应显著大于1.25 mmol/L时。然而,在糖尿病主动脉中,细胞外钙离子浓度的变化对收缩反应无显著影响。此外,非糖尿病主动脉对每种激动剂的收缩反应明显大于糖尿病主动脉。目前的结果表明,糖尿病血管的收缩对细胞外钙离子浓度的变化无反应,提示钙离子相关机制可能存在某种损伤。