Montamat S C, Olson R D, Mudumbi R V, Vestal R E
Clinical Pharmacology and Gerontology Research Unit, Department of Veterans Affairs Medical Center, Boise, Idaho, USA.
J Gerontol A Biol Sci Med Sci. 1996 Jul;51(4):B239-46. doi: 10.1093/gerona/51a.4.b239.
Adenosine, an endogenously produced nucleoside, has direct negative chronotropic and inotropic effects on right and left atrial tissues, respectively. Age-related differences in the effects of A1 adenosine receptor activation on atrial rhythmic and contractile function were investigated in adult (6-8 months) and senescent (23-24 months) Fischer 344 (F344) rats. Senescent right atria (RA) were more sensitive to the negative chronotropic effects of R-phenylisopropyladenosine (R-PIA), a selective A1 receptor agonist, than adult RA (EC50: 4.8 +/- 0.7 vs 10.8 +/- 1.5 nM). However, senescent left atria (LA) were 15.4% less responsive to the maximal negative inotropic effects of R-PIA than adult LA. R-PIA did not significantly change resting force from basal values in either age group, but 90% relaxation time was prolonged threefold in senescent LA compared with adults. Radioligand binding experiments with 1,3-[3H]dipropyl-8-cyclopentylxanthine, a selective adenosine A1 receptor antagonist, showed a 56% greater density (Bmax) of adenosine A1 receptor in senescent than adult without differences in affinities (Kd). The increased sensitivity of senescent RA to the negative chronotropic effects of adenosine A1 receptor stimulation suggests a role for adenosine in abnormal sinus node function that occurs more frequently with age. Adenosine A1 receptor stimulation has more effect on relaxation than contraction in senescent LA compared with LA from adult F344 rats. However, the increase in density of adenosine A1 receptors suggests a functional dissociation between the availability of binding sites and receptor activation.
腺苷是一种内源性产生的核苷，分别对右心房和左心房组织有直接的负性变时和变力作用。研究了成年（6 - 8个月）和衰老（23 - 24个月）的Fischer 344（F344）大鼠中，A1腺苷受体激活对心房节律和收缩功能影响的年龄相关差异。衰老的右心房（RA）对选择性A1受体激动剂R-苯异丙基腺苷（R-PIA）的负性变时作用比成年右心房更敏感（半数有效浓度：4.8±0.7对10.8±1.5 nM）。然而，衰老的左心房（LA）对R-PIA的最大负性变力作用的反应性比成年左心房低15.4%。R-PIA在两个年龄组中均未使静息力与基础值有显著变化，但与成年左心房相比，衰老左心房的90%舒张时间延长了两倍。用选择性腺苷A1受体拮抗剂1,3-[3H]二丙基-8-环戊基黄嘌呤进行的放射性配体结合实验表明，衰老大鼠腺苷A1受体的密度（Bmax）比成年大鼠高56%，而亲和力（Kd）无差异。衰老右心房对腺苷A1受体刺激的负性变时作用敏感性增加，提示腺苷在随年龄更频繁发生的异常窦房结功能中起作用。与成年F344大鼠的左心房相比，腺苷A1受体刺激对衰老左心房舒张的影响比对收缩的影响更大。然而，腺苷A1受体密度的增加表明结合位点的可用性与受体激活之间存在功能解离。
