Repeated daily injections and osmotic pump infusion of isoproterenol cause similar increases in cardiac mass but have different effects on blood pressure
Repeated daily injections and osmotic pump infusion of isoproterenol cause similar increases in cardiac mass but have different effects on blood pressure
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DOI：
10.1139/y04-137
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发表时间：
2005-02-01
影响因子：
2.1
通讯作者：
Hatton, DC
中科院分区：
文献类型：
--
作者：
Hohimer, AR;Davis, LE;Hatton, DC
我们发现，在小鼠中，每天重复一次皮下（s.c.）异丙肾上腺素（ISO）注射，如使用渗透微型泵的恒定输注，引起双心室质量或相对于体重的重量（VW/BW）增加。我们发现，5（1/d）s.c.注射2、10或20 μ g/g体重引起的VW/BW增加与以20 μ g/（g.d）输注5天相比相等）。虽然通常认为ISO通过对肌细胞的直接影响来促进肥大，但生长也可能继发于全身血流动力学效应。ISO的2种给药方式对平均动脉血压（MABP）和心率的影响不同。使用遥测技术，我们观察到单次注射ISO（0，0.5，2和10 μ g/g）与低血压和心动过速相关，持续时间但幅度不依赖于剂量。在最高剂量下，MABP迅速下降至60 mm Hg，超过2 μ l。恒定s.c. ISO以20 μ g/（g.d）输注，最初使MABP降至约70转Hg，持续24小时。在48小时MABP是正常的，但上升10毫米汞柱高于基线的第5天。因此，引起VW/BW相当增加的ISO的不同给药途径对MABP具有不同的影响。因此，当评价ISO诱导的心脏肥大的小鼠模型时，每日重复注射或输注均可引起VW/BW的相似增加，但所需的每日剂量不同。此外，这些不同的给药途径具有不同的血流动力学后遗症，并可能引起不同的心脏表型。
We found in mice that repeated single daily subcutaneous (s.c.) isoproterenol (ISO) injections, like constant infusions using osmotic minipumps, caused increased biventricular mass or weight relative to body weight (VW/BW). We found that 5 (1/d) s.c. injections of 2, 10, or 20 mu g/g body weight caused equivalent VW/BW increases as compared with 5-d infusions at 20 mu g/(g.d)). While it is often presumed that ISO elicits hypertrophy by a direct effect on the myocytes, growth may also be secondary to systemic hemodynamic effects. The 2 modes of ISO administration had different effects on mean arterial blood pressure (MABP) and heart rate. Using telemetry we observed that single injections of ISO (0, 0.5, 2, and 10 mu g/g) were associated with hypotension and tachycardia with a duration but not a magnitude that was dose dependent. MABP dropped rapidly to 60 mm Hg for more than 2 It at the highest dose. Constant s.c. infusion of ISO at 20 mu g/(g.d) initially lowered MABP to about 70 turn Hg for 24 h. At 48 h MABP was normal, but rose 10 mm Hg higher than baseline by day 5. Thus, different routes of administration of ISO that cause comparable increases in VW/BW had different effects on MABP. Thus when evaluating mouse models of ISO-induced cardiac hypertrophy, both repeated daily injections or infusions can cause similar increases in VW/BW, but the daily doses that are required are not the same. Furthermore, these different routes of administration have different hemodynamic sequelae and could potentially evoke different cardiac phenotypes.