Aoki K, Kikuchi K, Yamaji I, Nishimura M, Honma C, Kobayakawa H, Yamamoto M, Kudoh C, Shimazaki M, Sakamoto T
Second Department of Internal Medicine, Sapporo Medical College, Japan.
Clin Exp Hypertens A. 1989;11 Suppl 1:403-9. doi: 10.3109/10641968909045447.
Our previous studies have shown that a suppressed pressure natriuresis may contribute to the hypertensive mechanism in patients with essential hypertension (EHT), particularly in low renin patients (LRH). In this study, in order to clarify the role of renal dopaminergic activity in the blunted natriuresis of LRH, the conversion of 1-dopa (DOPA) to dopamine (DA) in the kidneys was investigated in 9 normotensive subjects (NT) and 20 EHT, including 15 normal renin EHT (NRH) and 5 LRH. All subjects were hospitalized and received a constant diet (Na:120mEq, K:75mEq daily). Plasma DOPA concentration (p-DOPA:HPLC-ECD), creatinine clearance (Ccr), urinary excretion of sodium (UNaV) and DA (UDA), as well as fractional excretion of sodium (FENa) were measured before and after the single oral administration of 1-DOPA (400mg). DOPA administration caused a significant increase of p-DOPA, UDA and FENa with undetectable DOPA levels in the urine in EHT. In addition, under the basal condition, UDA correlated positively with p-DOPA or the product of p-DOPA x Ccr, which might reflect the DOPA delivery at the renal proximal tubule. No significant difference was found in p-DOPA and the product of p-DOPA x Ccr among NT, NRH and LRH. However, the ratio of UDA/(p-DOPA x Ccr), which may indicate the conversion from DOPA to DA in the kidneys, was lower in EHT, especially in LRH, than that in NT. These results suggest that a reduced renal conversion from DOPA to DA may contribute to the attenuated natriuresis as well as renal dopaminergic activity in LRH.
我们之前的研究表明，压力性利钠作用受抑制可能在原发性高血压（EHT）患者的高血压机制中起作用，尤其是在低肾素患者（LRH）中。在本研究中，为了阐明肾多巴胺能活性在LRH利钠作用减弱中的作用，我们在9名血压正常的受试者（NT）和20名EHT患者（包括15名正常肾素EHT患者（NRH）和5名LRH患者）中研究了肾脏中左旋多巴（DOPA）向多巴胺（DA）的转化。所有受试者均住院并接受固定饮食（钠：每日120mEq，钾：每日75mEq）。在单次口服1 - DOPA（400mg）前后，测量血浆DOPA浓度（p - DOPA：高效液相色谱 - 电化学检测法）、肌酐清除率（Ccr）、尿钠排泄量（UNaV）和DA（UDA）以及钠排泄分数（FENa）。给予DOPA后，EHT患者的p - DOPA、UDA和FENa显著增加，且尿中未检测到DOPA水平。此外，在基础状态下，UDA与p - DOPA或p - DOPA×Ccr的乘积呈正相关，这可能反映了肾近端小管处的DOPA输送情况。NT、NRH和LRH之间的p - DOPA以及p - DOPA×Ccr的乘积未发现显著差异。然而，EHT患者，尤其是LRH患者中，UDA /（p - DOPA×Ccr）的比值（可能表明肾脏中从DOPA到DA的转化）低于NT患者。这些结果表明，LRH患者中肾脏从DOPA到DA的转化减少可能导致利钠作用减弱以及肾多巴胺能活性降低。
