L-ARGININE ABROGATES SALT-SENSITIVE HYPERTENSION IN DAHL RAPP RATS

L-ARGININE ABROGATES SALT-SENSITIVE HYPERTENSION IN DAHL RAPP RATS
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DOI:
10.1172/jci115467
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发表时间:
1991-11-01
影响因子:
15.9
通讯作者:
SANDERS, PW
SANDERS, PW
中科院分区:
医学1区
文献类型:
--
作者:
CHEN, PY;SANDERS, PW

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本研究探讨了一氧化氮(NO)的贡献的敏感性或抵抗高氯化钠(8.0%NaCl)摄入高血压的影响,在年轻的Dahl/Rapp盐敏感(SS/Jr)和盐耐(SR/Jr)大鼠。用N(G)-单甲基-L-精氨酸(L-NMMA)作为体内NO生成的探针,我们发现增加饮食中氯化钠可增加耐盐大鼠的NO活性,但对盐敏感大鼠无影响。外源性L-精氨酸(NO合成的底物)可使盐敏感大鼠的血压降至正常水平。D-精氨酸对上述大鼠血压无影响,L-精氨酸对耐盐大鼠血压无影响。腹膜内注射L-精氨酸及其前体L-瓜氨酸和口服L-精氨酸(但不是D-精氨酸)可防止高盐饮食盐敏感大鼠在观察2周内血压升高。相反,L-精氨酸并没有改变自发性高血压大鼠高血压的发展。口服L-精氨酸的盐敏感大鼠的平均尿cGMP水平高于口服D-精氨酸的盐敏感大鼠。两组患者输注L-NMMA后尿cGMP急剧下降,而静脉注射L-精氨酸后尿cGMP迅速升高。L-精氨酸和L-瓜氨酸可增加Dahl/Rapp大鼠NO的产生,并预防盐敏感性高血压。
This study examined the contribution of nitric oxide (NO) to the susceptibility or resistance to the hypertensive effects of high sodium chloride (8.0% NaCl) intake in young Dahl/Rapp salt-sensitive (SS/Jr) and salt-resistant (SR/Jr) rats. Using N(G)-monomethyl-L-arginine (L-NMMA) as a probe for NO production in vivo, we found that increasing dietary sodium choride increased NO activity in salt-resistant rats, but not in salt-sensitive rats. Exogenous L-arginine, the substrate for NO synthesis, decreased blood pressure to normotensive levels in salt-sensitive rats made hypertensive for 2 wk from 8.0% NaCl chow. D-Arginine had no effect on blood pressure of these rats and L-arginine did not change blood pressure of salt-resistant rats. Intraperitoneal injections Of L-arginine and its precursor, L-citrulline, and oral L-arginine, but not D-arginine, prevented the increase in blood pressure in salt-sensitive rats on the high salt chow over 2 wk of observation. In contrast, L-arginine did not alter the development of hypertension in spontaneously hypertensive rats. Mean urinary cGMP levels were higher in salt-sensitive rats on oral L-arginine than salt-sensitive rats on D-arginine. Infusion of L-NMMA acutely decreased, whereas intravenous L-arginine rapidly increased, urinary cGMP in both groups. L-Arginine and L-citrulline increased production of NO and prevented salt-sensitive hypertension in Dahl/Rapp rats.