Passmore John C, Joshua Irving G, Rowell Peter P, Tyagi Suresh C, Falcone Jeff C
Department of Physiology and Biophysics, School of Medicine, University of Louisville, Louisville, Kentucky 40292, USA.
J Cell Biochem. 2005 Nov 1;96(4):672-81. doi: 10.1002/jcb.20581.
As human males age, a decline in baroreflex-mediated elevation of blood pressure occurs due, at least in part, to a reduction in alpha-1 adrenergic vasoconstrictor function. Alpha adrenergic constriction is mediated by guanosine triphosphate binding Protein (G Protein) coupled signaling pathways. Alpha-1 A/C, B, and D adrenergic receptor expressions, measured by GeneChip array, are not reduced during aging in renal blood vessels of male or female rats. Alpha-1 A GeneChip expression is greater, at all ages studied, in females than in males. Prazosin binding by alpha-1 adrenergic receptors is greater in young adult female rats than in young adult male rats; however, it is reduced with aging in both male and female rats. G alpha q GeneChip expression declines while expression of adrenergic receptor kinase (GRK2) and tyrosine phosphatases (TyrP) increase with aging in male rats. The declines in alpha-1 adrenergic receptor binding and G alpha q expression and also the increases in GRK2 and TyrP expression likely relate to the age-related decline of vasoconstriction in male rats. The information that the expression of alpha-1 A adrenergic receptors is greater in female rats and (GRK2) expression does not increase during aging could relate to the gender differences in vasoconstrictor function with aging. Gene therapy to ameliorate the age-related decline in renal function could possibly reduce the need for renal dialysis. Signaling pathways such as those reviewed herein may provide an outline of the molecular pathways needed to move toward successful renal gene therapy for aging individuals.
随着男性年龄的增长，压力反射介导的血压升高会出现下降，至少部分原因是α-1肾上腺素能血管收缩功能的降低。α肾上腺素能收缩是由鸟苷三磷酸结合蛋白（G蛋白）偶联信号通路介导的。通过基因芯片阵列测量，α-1 A/C、B和D肾上腺素能受体的表达在雄性或雌性大鼠的肾血管衰老过程中并未降低。在所有研究的年龄段，雌性大鼠的α-1 A基因芯片表达均高于雄性大鼠。年轻成年雌性大鼠的α-1肾上腺素能受体与哌唑嗪的结合能力高于年轻成年雄性大鼠；然而，在雄性和雌性大鼠中，这种结合能力都会随着年龄的增长而降低。雄性大鼠中，Gαq基因芯片表达下降，而肾上腺素能受体激酶（GRK2）和酪氨酸磷酸酶（TyrP）的表达随年龄增长而增加。α-1肾上腺素能受体结合能力和Gαq表达的下降，以及GRK2和TyrP表达的增加，可能与雄性大鼠血管收缩功能随年龄增长的下降有关。雌性大鼠中α-1 A肾上腺素能受体表达较高且衰老过程中（GRK2）表达不增加这一信息，可能与血管收缩功能随年龄增长的性别差异有关。改善肾功能与年龄相关下降的基因治疗可能会减少肾透析的需求。本文所综述的信号通路可能为针对老年个体成功进行肾脏基因治疗所需的分子通路提供一个概述。
