Angiotensin II AT1 receptor blockade selectively enhances brain AT2 receptor expression, and abolishes the cold-restraint stress-induced increase in tyrosine hydroxylase mRNA in the locus coeruleus of spontaneously hypertensive rats
Angiotensin II AT1 receptor blockade selectively enhances brain AT2 receptor expression, and abolishes the cold-restraint stress-induced increase in tyrosine hydroxylase mRNA in the locus coeruleus of spontaneously hypertensive rats
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DOI：
10.1080/10253890801892040
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发表时间：
2008-01-01
影响因子：
2.3
通讯作者：
Saavedra, J. M.
中科院分区：
文献类型：
--
作者：
Bregonzio, C.;Seltzer, A.;Saavedra, J. M.
应激敏感的自发性高血压大鼠在接受2 h冷束缚应激前，用AT(1)受体拮抗剂坎地沙坦预先灌胃14天。非应激大鼠正中隆起和杏仁基底外侧核AT(1)受体结合减少，下橄榄内侧亚核AT(2)受体结合增加，丘脑腹外侧核AT(2)结合减少，蓝斑酪氨酸羟化酶mRNA水平升高。在非应激大鼠，AT(1)受体阻断减少了所有研究区域的AT(1)受体结合，并增强了下橄榄内侧亚核的AT(2)受体结合。坎地沙坦预处理可使应激后大鼠脑内AT(1)受体结合量降低，并可阻止应激所致丘脑腹外侧核内AT(2)受体结合量的减少。在蓝斑和肾上腺髓质，AT(1)阻断可消除应激引起的酪氨酸羟基酶mRNA水平的升高。我们的结果表明，口服坎地沙坦有效地阻断了脑AT(1)受体，选择性地增加了中枢AT(2)受体的表达，并阻止了应激诱导的中枢性酪氨酸羟化酶转录的刺激。这些结果支持脑AT(1)和AT(2)受体在应激反应调节中的作用，以及AT(1)受体拮抗剂除了具有抗高血压作用外，还可能被认为是治疗应激相关疾病的潜在化合物的假说。
Spontaneously hypertensive rats, a stress-sensitive strain, were pretreated orally for 14 days with the AT(1) receptor antagonist candesartan before submission to 2 h of cold-restraint stress. In non-treated rats, stress decreased AT(1) receptor binding in the median eminence and basolateral amygdala, increased AT(2) receptor binding in the medial subnucleus of the inferior olive, decreased AT(2) binding in the ventrolateral thalamic nucleus and increased tyrosine hydroxylase mRNA level in the locus coeruleus. In non-stressed rats, AT(1) receptor blockade reduced AT(1) receptor binding in all areas studied and enhanced AT(2) receptor binding in the medial subnucleus of the inferior olive. Candesartan pretreatment produced a similar decrease in brain AT(1) binding after stress, and prevented the stress-induced AT(2) receptor binding decrease in the ventrolateral thalamic nucleus. In the locus coeruleus and adrenal medulla, AT(1) blockade abolished the stress-induced increase in tyrosine hydroxylase mRNA level. Our results demonstrate that oral administration of candesartan effectively blocked brain AT(1) receptors, selectively increased central AT(2) receptor expression and prevented the stress-induced central stimulation of tyrosine hydroxylase transcription. The present results support a role of brain AT(1) and AT(2) receptors in the regulation of the stress response, and the hypothesis that AT(1) receptor antagonists may be considered as potential therapeutic compounds in stress related disorders in addition to their anti-hypertensive properties.