Role of vasoconstrictor systems in experimental glucocorticoid-hypertension in rats.
Role of vasoconstrictor systems in experimental glucocorticoid-hypertension in rats.
复制标题
血管收缩系统在大鼠实验性糖皮质激素高血压中的作用。
DOI：
10.1042/cs0650255
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发表时间：
1983
期刊：
影响因子：
--
通讯作者：
Brunner,HR
中科院分区：
文献类型：
--
作者：
Waeber,B;Gavras,H;Bresnahan,MR;Gavras,I;Brunner,HR
1. SKF 64139是一种作用于中枢和外周神经系统的苯乙醇胺N-甲基转移酶（PNMT）抑制剂，在清醒的正常血压大鼠和糖皮质激素高血压大鼠中研究了SKF 64139对血压的影响，这些大鼠在缺盐饮食条件下维持2周。实验当天，正常血压大鼠的平均血压为119.2 ± 1.1mmHg（mean ± sem），高血压大鼠为143.2 ± 1.9mmHg（P< 0.001）。在所有动物中，经口灌胃SKF 64139（50 mg/kg）或其溶剂（5%葡萄糖溶液）后，对血压进行4小时跟踪。2.在溶剂处理的大鼠中，未发生血压变化。然而，SKF 64139给药后，高血压大鼠的血压下降了17.9 ± 3.8 mmHg（P< 0.001），而正常血压动物的血压没有下降。在观察期结束时测定所有这些大鼠的血浆儿茶酚胺。在正常血压和高血压大鼠以及溶剂和SKF 64139治疗大鼠之间未观察到血浆去甲肾上腺素和肾上腺素水平的显著差异，但在给予PNMT载体后，两种儿茶酚胺均趋于升高。在另外两组糖皮质激素-高血压大鼠中，输注saralasin（血管紧张素II的竞争性拮抗剂）或推注拮抗加压素的升压作用的加压素类似物的血压效应，加压素拮抗剂对血压没有影响，而saralasin使平均血压从144 ±1.9降至136 ± 1.9。3.2mmHg（P< 0.005）。这些数据表明，交感神经系统是参与维持已建立的糖皮质激素性高血压的主要血管收缩系统。由于SKF 64139也已知在一定程度上抑制α-肾上腺素受体、单胺氧化酶和神经元摄取过程，但尚不清楚这种PNMT抑制剂的降压作用是否可归因于肾上腺素合成的中枢阻滞。
1. The blood pressure effect of SKF 64139, a phenylethanolamineN-methyltransferase (PNMT) inhibitor acting both in the central and peripheral nervous system, was studied in conscious normotensive and glucocorticoid-hypertensive rats maintained for 2 weeks on a salt-deficient diet. On the day of the experiment, mean blood pressure was 119.2 ± 1.1 mmHg (mean ± sem) in the normotensive and 143.2 ± 1.9 mmHg (P< 0.001) in the hypertensive rats. In all animals, the blood pressure was followed for 4 h after oral gavage by either SKF 64139 (50 mg/kg) or its vehicle (5% glucose solution).2. In the vehicle-treated rats, no change in blood pressure occurred. However, after SKF 64139 administration, a 17.9 ± 3.8 mmHg (P< 0.001) blood pressure fall was observed in the hypertensive rats whereas normotensive animals did not decrease their pressure.3. Plasma catecholamines were determined in all these rats at the end of the observation period. No significant difference in plasma noradrenaline and adrenaline levels was observed between normotensive and hypertensive as well as vehicle- and SKF 64139-treated rats, though both catecholamines tended to be higher after administration of the PNMT inhibitor.4. In two additional groups of glucocorticoid-hypertensive rats, the blood pressure effects of an infusion of saralasin, a competitive antagonist of angiotensin II, or of a bolus injection of a vasopressin analogue antagonizing the pressor action of vasopressin, were investigated over a 20 min period.The vasopressin antagonist had no blood pressure effect whereas saralasin decreased mean blood pressure from 144 ±1.9 to 136 ± 3.2 mmHg (P< 0.005).5. These data suggest that the sympathetic nervous system is the main vasoconstrictor system involved in the maintenance of established glucocorticoid hypertension. Since SKF 64139 is also known to inhibit to some degree α-adrenoceptors, monoamine oxidase and neuronal uptake processes, it remains unclear, however, whether the blood pressure-lowering effect of this PNMT inhibitor can be attributed to central blockade of adrenaline synthesis.