Influence of sympathetic and AT1-receptor blockade on angiotensin II and adrenergic agonist-induced renal vasoconstrictions in spontaneously hypertensive rats
Influence of sympathetic and AT1-receptor blockade on angiotensin II and adrenergic agonist-induced renal vasoconstrictions in spontaneously hypertensive rats
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DOI：
10.1111/j.1748-1716.2008.01895.x
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发表时间：
2009-03-01
影响因子：
6.3
通讯作者：
Johns, E. J.
中科院分区：
文献类型：
--
作者：
Abdulla, M. H.;Sattar, M. A.;Johns, E. J.
本研究观察了血管紧张素Ⅱ（Ang Ⅱ）受体和肾上腺素能受体阻滞剂对自发性高血压大鼠（SHR）肾血管收缩的影响。卡维地洛（5 mg kg（-1）天（-1）p.o.）或氯沙坦+卡维地洛（10 mg kg（-1）day（-1）+ 5 mg kg（-1）day（-1）p.o.）。在第8天，麻醉大鼠并进行肾血管收缩实验。一组大鼠行急性去肾神经损伤，氯沙坦和卡维地洛治疗后，去甲肾上腺素、苯肾上腺素、甲氧胺和Ang Ⅱ的肾血管收缩反应均较未治疗组显著降低（P <0.05）。然而，在去肾神经SHR与卡维地洛治疗，血管收缩反应增强与完整的肾神经SHR与卡维地洛治疗相比，所有的血管活性药物。与单独给予氯沙坦或卡维地洛相比，给予氯沙坦和卡维地洛的完整SHR对血管活性药物的肾血管收缩反应更强卡维地洛可降低肾神经对Ang Ⅱ和所有肾上腺素能激动剂的血管收缩反应，但在去除肾交感神经活性后，卡维地洛增强肾α 1肾上腺素受体和AT 1受体对血管活性药物的敏感性。联合治疗氯沙坦和卡维地洛减少肾血管收缩反应外源性给药的血管活性药物，但在较小程度上比氯沙坦或卡维地洛单独。所获得的结果表明，在SHR的血管紧张素Ⅱ受体和肾上腺素能神经传递之间的相互作用。
This study investigated the influence of angiotensin II (Ang II) receptor and adrenergic blockade on the renal vasoconstrictions caused by Ang II and adrenergic agonists in spontaneously hypertensive rats (SHR).Forty-eight SHR were subjected to 7 days of losartan (10 mg kg(-1) day(-1) p.o.), carvedilol (5 mg kg(-1) day(-1) p.o.) or losartan + carvedilol (10 mg kg(-1) day(-1) + 5 mg kg(-1) day(-1) p.o.). On day 8, the rats were anaesthetized and renal vasoconstrictor experiments performed. One group of rats underwent acute unilateral renal denervation.There were significant (P < 0.05) reductions in the renal vasoconstrictor responses to noradrenaline, phenylephrine, methoxamine and Ang II after losartan and carvedilol treatments compared with that in untreated rats (all P < 0.05). However, in renally denervated SHR treated with carvedilol, the vasoconstrictor responses to all the vasoactive agents were enhanced compared with those in SHR with intact renal nerves treated with carvedilol. Intact SHR given both losartan and carvedilol showed greater renal vasoconstrictor responses to the vasoactive agents than when given either losartan or carvedilol alone (all P < 0.05).Carvedilol reduced the vasoconstrictor response to Ang II and all the adrenergic agonists in the presence of the renal nerves, but, following the removal of renal sympathetic activity, carvedilol enhanced the sensitivity of both renal alpha(1)-adrenoceptors and AT(1) receptors to the vasoactive agents. Co-treatment with losartan and carvedilol reduced the renal vasoconstrictor responses to exogenously administered vasoactive agents but to a lesser extent than losartan or carvedilol alone. The results obtained demonstrate an interaction between Ang II receptors and adrenergic neurotransmission in the SHR.