Mutafova-Yambolieva V, Staneva-Stoytcheva D, Lasova L, Radomirov R
Department of Experimental Pharmacology, Bulgarian Academy of Sciences, Sofia.
Pharmacology. 1994 Feb;48(2):100-10. doi: 10.1159/000139168.
Subchronic (30 days) exposure of rats to Co(NO3)2 or NiSO4 (20 mg.kg-1) in drinking water caused suppression of the isolated vas deferens contractile responses to exogenous adenosine 5'-triphosphate (ATP), noradrenaline, and l-phenylephrine, shifting the concentration-response curves to the relevant agonist to the right. Both metals facilitated the alpha 1-adrenoceptor antagonistic effects of prazosin, which resulted in increased pA2 values for the drug (9.68 +/- 0.13 in controls vs. 10.15 +/- 0.12 in Co(2+)-treated preparations and 12.60 +/- 0.67 in Ni(2+)-treated preparations). The inhibitory effect of clonidine on the contractions in response to low-frequency electrical field stimulation (EFS) in metal-treated preparations was decreased with pD2 values: 10.52 +/- 0.04 in controls, 9.56 +/- 0.13 in Co(2+)-treated preparations and 9.92 +/- 0.16 in Ni(2+)-treated preparations. The monophasic contractile responses to low-frequency EFS (0.1 Hz, 1 ms, 80 V) as well as the first phase of the biphasic contractions after high-frequency long-lasting EFS (300 pulses, 0.1 ms, 40 V, at 4, 8 or 20 Hz) were significantly increased in both groups of heavy metal-treated preparations. Therefore, subchronic exposure to Co2+ or Ni2+ leads to changes in pre- and postjunctional mechanisms underlying the sympathetically mediated contractile activity of isolated rat vas deferens.
大鼠在饮用水中连续30天接触硝酸钴(Co(NO3)2)或硫酸镍(NiSO4)(20毫克/千克)会导致离体输精管对外源性5'-三磷酸腺苷(ATP)、去甲肾上腺素和苯肾上腺素的收缩反应受到抑制,使相关激动剂的浓度-反应曲线右移。两种金属都增强了哌唑嗪的α1-肾上腺素能受体拮抗作用,导致该药物的pA2值增加(对照组为9.68±0.13,钴(2+)处理组制剂为10.15±0.12,镍(2+)处理组制剂为12.60±0.67)。可乐定对金属处理组制剂中低频电场刺激(EFS)引起的收缩的抑制作用减弱,其pD2值分别为:对照组10.52±0.04,钴(2+)处理组制剂9.56±0.13,镍(2+)处理组制剂9.92±0.16。在两组重金属处理组制剂中,对低频EFS(0.1赫兹,1毫秒,80伏)的单相收缩反应以及高频长时间EFS(300个脉冲,0.1毫秒,40伏,4、8或20赫兹)后的双相收缩的第一相均显著增加。因此,连续30天接触钴2+或镍2+会导致大鼠离体输精管交感神经介导的收缩活动的节前和节后机制发生变化。