Faculty of Physical Education and Recreation, Univ. of Alberta, P-320-P Van Vliet Centre, Edmonton, Alberta T6G 2H9 Canada.
Am J Physiol Regul Integr Comp Physiol. 2010 Nov;299(5):R1342-9. doi: 10.1152/ajpregu.00194.2010. Epub 2010 Aug 11.
We tested the hypothesis that tonic adrenergic and nonadrenergic receptor-mediated sympathetic vasoconstriction would increase at rest and during exercise with advancing age. Young (n = 6; 22 ± 1 mo; means ± SE) and old (n = 6; 118 ± 9 mo) beagles were studied. Selective antagonists for alpha-1, alpha-2, neuropeptide Y (NPY), and purinergic (P(2x)) receptors were infused at rest and during treadmill running at 2.5 mph and 4 mph with 2.5% grade. Prazosin produced similar increases in vascular conductance in young and old beagles at rest (Young: 158 ± 34%; Old: 98 ± 19%) and during exercise at 2.5 mph (Young: 80 ± 10%; Old: 58 ± 12%) and 4 mph and 2.5% grade (Young: 57 ± 5%; Old: 26 ± 4%). Rauwolscine caused similar (P > 0.05) increases in vascular conductance in old compared with young dogs at rest (Young: 119 ± 25%; Old: 64 ± 22%) and at 2.5 mph (Young: 86 ± 13%; Old: 60 ± 7%) and 4 mph with 2.5% grade (Young: 61 ± 5%; Old: 43 ± 7%). N2-(diphenylacetyl)-N-[4-hydroxyphenyl)methyl]-d-arginine amide (BIBP) caused a smaller increase (P < 0.05) in vascular conductance in old compared with young dogs at rest (Young: 179 ± 44%; Old: 91 ± 22%), whereas similar increases (P > 0.05) of experimental limb vascular conductance in young and old dogs occurred following BIBP during exercise at 2.5 mph (Young: 56 ± 16%; Old: 50 ± 12%) and 4 mph and 2.5% grade (Young: 45 ± 10%; Old: 25 ± 7%). Pyridoxal-phosphate-6-azophenyl-2'-4'-disulfonic acid infusion produced a larger increase in vascular conductance in old compared with young beagles at rest (Young: 88 ± 14%; Old: 191 ± 58%), whereas similar increases were observed at 2.5 mph (Young: 47 ± 18%; Old: 31 ± 11%) and 4 mph with 2.5% grade (Young: 26 ± 13%; Old: -18 ± 8%). At rest, NPY receptor-mediated restraint of skeletal muscle blood flow was reduced with advancing age, whereas P(2x) receptor-mediated restraint of skeletal muscle blood flow was increased. During exercise, the magnitude of adrenergic and nonadrenergic sympathetic vasoconstriction was not different between young and old dogs. Overall, these data demonstrate that adrenergic receptor-mediated vasoconstriction was not elevated at rest, but nonadrenergic sympathetic vasoconstriction was altered under basal conditions in aged beagles.
我们测试了这样一个假设,即在衰老过程中,紧张性肾上腺素能和非肾上腺素能受体介导的交感血管收缩在休息和运动时会增加。年轻(n = 6;22 ± 1 个月;平均值 ± SE)和老年(n = 6;118 ± 9 个月)比格犬被研究。在休息时和在 2.5 英里/小时和 4 英里/小时的跑步机上以 2.5%的坡度跑步时,输注了用于选择性拮抗 alpha-1、alpha-2、神经肽 Y(NPY)和嘌呤能(P(2x))受体的拮抗剂。普萘洛尔在休息时和在 2.5 英里/小时、4 英里/小时和 2.5%坡度的运动时,在年轻和老年比格犬中引起相似的血管传导增加(年轻:158 ± 34%;老年:98 ± 19%)。在休息时(年轻:119 ± 25%;老年:64 ± 22%)和在 2.5 英里/小时(年轻:86 ± 13%;老年:60 ± 7%)和 4 英里/小时和 2.5%坡度(年轻:61 ± 5%;老年:43 ± 7%),Rauwolscine 在老年犬中引起的血管传导增加与年轻犬相似。N2-(二苯乙酰基)-N-[4-羟基苯基)甲基]-d-精氨酸酰胺(BIBP)在休息时(年轻:179 ± 44%;老年:91 ± 22%)引起的血管传导增加较小,与年轻犬相比,老年犬的BIBP 在运动时(年轻:56 ± 16%;老年:50 ± 12%)和 4 英里/小时和 2.5%坡度(年轻:45 ± 10%;老年:25 ± 7%)引起的实验性肢体血管传导增加相似。吡哆醛-6-偶氮苯-2'-4'-二磺酸灌注在休息时(年轻:88 ± 14%;老年:191 ± 58%)引起的血管传导增加大于老年比格犬,而在 2.5 英里/小时(年轻:47 ± 18%;老年:31 ± 11%)和 4 英里/小时和 2.5%坡度(年轻:26 ± 13%;老年:-18 ± 8%)时观察到相似的增加。在休息时,随着年龄的增长,NPY 受体介导的骨骼肌血流限制减少,而 P(2x)受体介导的骨骼肌血流限制增加。在运动时,年轻和老年犬的肾上腺素能和非肾上腺素能交感血管收缩的幅度没有差异。总的来说,这些数据表明,在休息时,肾上腺素能受体介导的血管收缩并没有升高,但在老年比格犬的基础条件下,非肾上腺素能交感血管收缩发生了改变。