Chronic infusion of angiotensin receptor antagonists in the hypothalamic paraventricular nucleus prevents hypertension in a rat model of sleep apnea.
Chronic infusion of angiotensin receptor antagonists in the hypothalamic paraventricular nucleus prevents hypertension in a rat model of sleep apnea.
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DOI：
10.1016/j.brainres.2010.10.087
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发表时间：
2011-01-12
期刊：
影响因子：
2.9
通讯作者：
Kanagy NL
中科院分区：
文献类型：
--
作者：
da Silva AQ;Fontes MA;Kanagy NL
睡眠呼吸暂停的特征是交感神经活动增加，并与系统性高血压有关。血管紧张素(Ang)参与了下丘脑室旁核(PVN)神经元的交感神经张力和动脉压的调节。在睡眠呼吸暂停诱导的高血压大鼠模型中，我们研究了下丘脑室旁核内内源性血管紧张素转换酶多肽在控制血压中的作用。雄性SD大鼠(250g)，经双侧导管靶向室旁核，给予血管紧张素转换酶拮抗剂(A-779，Ang-(1-7)拮抗剂；氯沙坦和ZD7155，AT1拮抗剂；PD123319，AT2受体拮抗剂，或生理盐水)。另一组接受GABAA受体激动剂(麝香酚)的输注，以抑制不依赖血管紧张素受体的PVN神经元活动。置管后，大鼠睡眠时暴露于间歇性低氧(IH；低谷5%O2；5%CO2至峰值21%O2；0%CO2)20个周期/小时，每天7小时，连续14天，同时遥测平均动脉压(MAP)。在接受生理盐水暴露的大鼠中，IH暴露显著增加MAP(+12±2 mm Hgvs Sham−2±1 mm HgP<；0.01)。用麝香酚抑制下丘脑室旁核神经元可逆转IH大鼠MAP的升高(MUS：−9±4 mm Hgvs VS VS 12±2 mm Hg；P<；0.0 1)。静脉注射任何一种血管紧张素转换酶拮抗剂均可阻断高血压引起的MAP升高(A-779：−5±1 mm Hg，−：9±4 mm Hg，ZD7155：−11±4 mm Hg，PD123319：−4±3 mm Hg；P<；0.01)。我们的结果表明，作用于下丘脑室旁核的内源性血管紧张素转换酶多肽有助于在这个睡眠呼吸暂停诱导性高血压大鼠模型中观察到IH诱导的MAP升高。
Sleep apnea is characterized by increased sympathetic activity and is associated with systemic hypertension. Angiotensin (Ang) peptides have previously been shown to participate in the regulation of sympathetic tone and arterial pressure in the hypothalamic paraventricular nucleus (PVN) neurons. We investigated the role of endogenous Ang peptides within the PVN to control blood pressure in a rat model of sleep apnea-induced hypertension. Male Sprague Dawley rats (250g), instrumented with bilateral guide cannulae targeting the PVN, received chronic infusion of Ang antagonists (A-779, Ang-(1-7) antagonist; losartan and ZD7155, AT1 antagonists; PD123319, AT2 receptor antagonist, or saline vehicle). A separate group received an infusion of the GABAA receptor agonist (muscimol) to inhibit PVN neuronal activity independent of angiotensin receptors. After cannula placement, rats were exposed during their sleep period to eucapnic intermittent hypoxia (IH; nadir 5% O2; 5% CO2 to peak 21% O2; 0% CO2) 20 cycles/hour, 7 hours/day, for 14 days while mean arterial pressure (MAP) was measured by telemetry. In rats receiving saline, IH exposure significantly increased MAP (+12±2 mmHg vs Sham −2±1 mmHg P<0.01). Inhibition of PVN neurons with muscimol reversed the increase in MAP in IH rats (MUS: −9±4 mmHg vs vehicle +12±2 mmHg; P<0.01). Infusion of any of the Ang antagonists also prevented the rise in MAP induced by IH (A-779: −5±1 mmHg, losartan: −9±4 mmHg, ZD7155: −11±4 mmHg and PD123319: −4±3 mmHg; P<0.01). Our results suggest that endogenous Ang peptides acting in the PVN contribute to IH-induced increases in MAP observed in this rat model of sleep apnea-induced hypertension.
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影响因子：
2.7
作者：
Braga, Valdir A.;Soriano, Renato N.;Machado, Benedito H.
通讯作者：
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影响因子：
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DOI：
10.1111/j.1440-1681.1996.tb02590.x
发表时间：
1996-02-01
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