Liu Kiao-Ling, Lo Ming, Benzoni Daniel
Département de Physiologie et Pharmacologie Clinique, Faculté de Pharmacie, Université Claude Bernard Lyon, 8 avenue Rockefeller, 69373 Lyon Cedex 08, France.
Am J Hypertens. 2006 Jun;19(6):617-22. doi: 10.1016/j.amjhyper.2005.12.015.
Early and chronic angiotensin converting enzyme (ACE) inhibition prevents hypertension and improves the pressure natriuresis in Lyon hypertensive (LH) rats. The effect of this treatment on the responses of renal medullary blood flow (MBF) to angiotensin II (Ang II) was studied.
In chronic experiments, Ang II (7.5 to 480 ng/kg, intravenous) was injected in 15-week-old anesthetized LH and normotensive (LL) control rats treated orally since weaning with perindopril (0.4 or 1.5 mg/kg/day) with or without pretreatment with indomethacin (5 mg/kg intravenous). In acute experiment, Ang II (30 to 480 ng/kg intravenous) was given in LH rats treated acutely with perindopril (1.5 mg/kg, intravenous bolus).
Administration of Ang II induced dose-dependent decreases in MBF, which were greater in LH than in LL rats. In LL rats, the initial and short-lasting (<1 min) medullary vasoconstriction evoked by Ang II was followed by a long-lasting (>2 min) and dose-dependent medullary vasodilation, which was blunted in LH rats. Chronic perindopril treatment normalized the blood pressure level in LH rats and corrected their blunted medullary vasodilation, whereas the same treatment had no significant effect in LL rats. In chronically perindopril-treated LH rats, indomethacin decreased by 90% the medullary vasodilation induced by Ang II. Acute perindopril treatment did not modify the medullary responses to Ang II in LH rats.
Chronic ACE inhibition restores the vasodilator response of MBF to Ang II in LH rats. This effect, which is not observed after acute inhibition, is mainly mediated through the release of prostaglandins.
早期及长期的血管紧张素转换酶（ACE）抑制可预防高血压，并改善里昂高血压（LH）大鼠的压力性利钠作用。本研究探讨了该治疗对肾髓质血流（MBF）对血管紧张素II（Ang II）反应的影响。
在慢性实验中，对15周龄经麻醉的LH大鼠和正常血压（LL）对照大鼠静脉注射Ang II（7.5至480 ng/kg），这些大鼠自断奶起口服培哚普利（0.4或1.5 mg/kg/天），部分大鼠在注射前静脉注射吲哚美辛（5 mg/kg）。在急性实验中，对急性接受培哚普利（1.5 mg/kg静脉推注）治疗的LH大鼠静脉注射Ang II（30至480 ng/kg）。
注射Ang II可引起MBF呈剂量依赖性降低，LH大鼠的降低幅度大于LL大鼠。在LL大鼠中，Ang II诱发的初始且短暂（<1分钟）的髓质血管收缩之后是持久（>2分钟）且剂量依赖性的髓质血管舒张，而LH大鼠的这种血管舒张减弱。长期培哚普利治疗可使LH大鼠的血压水平恢复正常，并纠正其减弱的髓质血管舒张，而相同治疗对LL大鼠无显著影响。在长期接受培哚普利治疗的LH大鼠中，吲哚美辛使Ang II诱导的髓质血管舒张降低了90%。急性培哚普利治疗未改变LH大鼠对Ang II的髓质反应。
长期ACE抑制可恢复LH大鼠MBF对Ang II的血管舒张反应。这种在急性抑制后未观察到的效应主要通过前列腺素的释放介导。
