Plasma l-[3H]norepinephrine, d-[14C]norepinephrine, and d,l-[3H]isoproterenol kinetics in essential hypertension.

Plasma l-[3H]norepinephrine, d-[14C]norepinephrine, and d,l-[3H]isoproterenol kinetics in essential hypertension.
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原发性高血压的血浆l-[3H]去甲肾上腺素、d-[14C]去甲肾上腺素和d,l-[3H]异丙肾上腺素动力学。

DOI:
10.1172/jci111134
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发表时间:
1983
期刊:
The Journal of clinical investigation
影响因子:
--
通讯作者:
I. Kopin
I. Kopin
中科院分区:
--
文献类型:
--
作者:
D. Goldstein;D. Horwitz;H. Keiser;R. Polinsky;I. Kopin

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我们将示踪剂标记的l-[3H]-去甲肾上腺素、d-[14C]去甲肾上腺素和d,l-[3H]-异丙肾上腺素同时注入原发性高血压患者和血压正常对照受试者体内,以确定这些物质的消失动力学异常是否是高血压患者的特征。高血压组的平均输注前静脉血浆去甲肾上腺素浓度稍高(260 vs. 194 pg/ml,P = 0.06),但各组在左旋或右旋去甲肾上腺素或异丙肾上腺素的消失动力学上没有差异。在高血压组和正常血压组中,输注前血浆去甲肾上腺素与计算的溢出率显着正相关,但与去甲肾上腺素清除率不相关。即使在用神经元去甲肾上腺素摄取阻滞剂地昔帕明预处理后,血浆去甲肾上腺素的 d/l 比率在输注期间和输注后与输注液中的相同。由于异丙肾上腺素不被神经末梢吸收,输注结束后[3H]异丙肾上腺素与l-[3H]去甲肾上腺素的比率增加。通过地昔帕明预处理,这种增加几乎完全消除。这些结果表明,(a)一些原发性高血压患者血浆去甲肾上腺素水平升高是由于交感神经活动增加,而不是去甲肾上腺素清除率降低所致,(b)同时输注异丙肾上腺素/去甲肾上腺素比率的变化提供了人类神经元去甲肾上腺素摄取的指数,(c)神经元去甲肾上腺素摄取不是立体特异性的。
We infused tracer-labeled l-[3H]-norepinephrine, d-[14C]norepinephrine, and d,l-[3H]-isoproterenol simultaneously into patients with essential hypertension and into normotensive control subjects, in order to determine whether abnormalities in the disappearance kinetics of these substances characterized the hypertensive patients. The mean preinfusion venous plasma norepinephrine concentration was somewhat higher in the hypertensive group (260 vs. 194 pg/ml, P = 0.06), but the groups did not differ in the disappearance kinetics of l- or d-norepinephrine or of isoproterenol. Preinfusion plasma norepinephrine was significantly positively correlated with calculated spillover rates in both the hypertensive and normotensive groups, but not with norepinephrine clearances. The d/l ratio in plasma norepinephrine was the same as in the infusate during and after the infusion, even after pretreatment with the neuronal norepinephrine uptake blocker, desipramine. Because isoproterenol is not taken up by nerve endings, the ratio of [3H]isoproterenol to l-[3H]norepinephrine increased after the infusion ended. This increase was almost completely abolished by pretreatment with desipramine. These results indicate that (a) increased plasma norepinephrine levels seen in some patients with essential hypertension result from increased sympathetic neural activity and not from decreased clearance of norepinephrine, (b) changes in the isoproterenol/norepinephrine ratio after simultaneous infusion of both provide an index of neuronal norepinephrine uptake in man, and (c) neuronal norepinephrine uptake is not stereospecific.