Robert A, Tran N N, Giummelly P, Atkinson J, Capdeville-Atkinson C
Laboratoire de Pharmacologie Cardio-vasculaire, Universite Henri Poincare, Faculte de Pharmacie, 54001 Nancy Cedex, France.
Am J Physiol. 1998 Jun;274(6):R1604-12. doi: 10.1152/ajpregu.1998.274.6.R1604.
In male Wistar rats, the in vitro vasoconstrictor response of the perfused tail artery elicited by norepinephrine or serotonin decreased with age (24 mo old vs. 3 mo old), whereas the fluorescent signal (fura 2) produced by intracellular calcium (Ca2+i) mobilization increased. Both vasoconstriction and the increase in intracellular calcium concentration elicited by a high-K+, depolarizing solution were unaffected by aging. Pertussis toxin, a G protein inhibitor, had no effect on vasoconstriction induced by high K+ but diminished vasoconstrictor responses to norepinephrine in 3- and 12-mo-old animals but not in 24-mo-old animals. Pertussis toxin had no effect on Ca2+i mobilization. The sensitivity of receptor activation to pertussis toxin in tail arteries from 24-mo-old animals was restored by pretreatment with the alpha-adrenoceptor antagonist nicergoline. Nicergoline had no effect on vasoconstriction induced by high K+. Plasma norepinephrine concentration rose with age; nicergoline had no effect on this rise. We suggest that aging leads to a decrease in the intracellular G protein-modulated amplification of vasoconstriction produced by receptor activation and that this could be linked to the hyperadrenergic state. Ca2+ sensitivity can be restored by chronic treatment with an alpha-adrenoceptor antagonist.
在雄性Wistar大鼠中，去甲肾上腺素或5-羟色胺引起的灌注尾动脉的体外血管收缩反应随年龄增长而降低（24月龄与3月龄相比），而细胞内钙（Ca2+ i）动员产生的荧光信号（fura 2）增加。高钾去极化溶液引起的血管收缩和细胞内钙浓度的增加均不受衰老影响。百日咳毒素是一种G蛋白抑制剂，对高钾诱导的血管收缩没有影响，但减弱了3月龄和12月龄动物对去甲肾上腺素的血管收缩反应，而对24月龄动物没有影响。百日咳毒素对Ca2+ i动员没有影响。用α-肾上腺素能受体拮抗剂尼麦角林预处理可恢复24月龄动物尾动脉中受体激活对百日咳毒素的敏感性。尼麦角林对高钾诱导的血管收缩没有影响。血浆去甲肾上腺素浓度随年龄增长而升高；尼麦角林对此升高没有影响。我们认为，衰老导致受体激活产生的血管收缩的细胞内G蛋白调节放大作用降低，这可能与高肾上腺素能状态有关。慢性给予α-肾上腺素能受体拮抗剂可恢复Ca2+ 敏感性。
