Schutzer W E, Xue H, Reed J F, Roullet J B, Anderson S, Mader S L
Research Service, Portland Veterans Affairs Medical Center, Portland, Oregon 97201, USA.
Am J Physiol Heart Circ Physiol. 2000 Dec;279(6):H2807-14. doi: 10.1152/ajpheart.2000.279.6.H2807.
beta-Adrenergic receptor (beta-AR)-mediated (cAMP-dependent) vasorelaxation declines with advancing age. It has been shown that angiotensin II (ANG II), a potent vasoconstrictor, enhances cAMP-mediated vasorelaxation. Therefore, we questioned whether ANG II could reverse age-related, impaired beta-AR-mediated vasorelaxation and cAMP production. Pretreatment of aortic rings from 6-wk-old or 6-mo-old male Fischer 344 rats with ANG II significantly enhanced vasorelaxation induced by isoproterenol (Iso), a beta-AR agonist, and forskolin, a direct activator of adenylyl cyclase, but not dibutyryl-cAMP or isobutylmethylxanthine. The ANG II effect was blocked by losartan but not PD-123319 and was not observed in the aortas from 12- and 24-mo-old animals. Iso-stimulated cAMP production in the aorta was enhanced in the presence of ANG II in the 6-wk-old and 6-mo-old age groups only. Results suggest ANG II cannot reverse the age-related impairment in beta-AR-dependent vasorelaxation. We conclude aging may affect a factor common to both ANG II-receptors and beta-AR signaling pathways or aging may impair cross-talk between these two receptor pathways.
β-肾上腺素能受体(β-AR)介导的(cAMP依赖性)血管舒张功能随年龄增长而下降。研究表明,强效血管收缩剂血管紧张素II(ANG II)可增强cAMP介导的血管舒张。因此,我们质疑ANG II是否能够逆转与年龄相关的、受损的β-AR介导的血管舒张和cAMP生成。用ANG II预处理6周龄或6月龄雄性Fischer 344大鼠的主动脉环,可显著增强β-AR激动剂异丙肾上腺素(Iso)和腺苷酸环化酶直接激活剂福斯可林诱导的血管舒张,但对二丁酰-cAMP或异丁基甲基黄嘌呤无此作用。ANG II的作用被氯沙坦阻断,但未被PD-123319阻断,且在12月龄和24月龄动物的主动脉中未观察到该作用。仅在6周龄和6月龄年龄组中,ANG II存在时主动脉中Iso刺激的cAMP生成增加。结果表明ANG II不能逆转与年龄相关的β-AR依赖性血管舒张功能受损。我们得出结论,衰老可能影响ANG II受体和β-AR信号通路共有的一个因素,或者衰老可能损害这两个受体通路之间的相互作用。