Vaskonen T, Mervaala E, Krogerus L, Teräväinen T L, Laakso J, Karppanen H, Vapaatalo H
Department of Pharmacology and Toxicology, University of Helsinki, Finland.
Hypertens Res. 1997 Sep;20(3):183-92. doi: 10.1291/hypres.20.183.
The cardiovascular effects of chronic inhibition of nitric oxide synthesis and dietary salt were studied in 9-wk-old spontaneously hypertensive rats (SHR). N omega-nitro-L-arginine methyl ester (L-NAME, 0.025% in food, about 20 mg/kg/d) was given to rats receiving diets containing low, moderate, and high salt levels (NaCl 0.2%, 1.1%, and 6.0% of the dry weight of the chow) for 3 wk, L-NAME increased systolic blood pressure by 50 to 60 mmHg in all treated groups, as compared with an average rise of 10 to 20 mmHg in the control SHR. The high-salt diet did not further increase blood pressure. L-NAME also induced cardiac and renal hypertrophy, and these changes were aggravated by the high-salt diet. In addition, 19 of the 30 rats treated with L-NAME suffered strokes and all of them had several myocardial infarctions and renal damage, while the rats not treated with L-NAME had no evidence of stroke or myocardial or renal injury. Responses of mesenteric arterial rings in vitro were studied at the end of the experiment. The vascular contractile responses to noradrenaline were increased, and the relaxation responses to acetylcholine were inhibited in the L-NAME treated groups. In addition, the high-salt diet alone tended to inhibit the response to acetylcholine. Plasma renin activity was markedly increased by L-NAME treatment and decreased by the high-salt diet. The 24-h urine protein excretion was increased both by the L-NAME treatment and by the high-salt diet. The combination of L-NAME and the high-salt diet markedly raised the serum creatinine concentration. Our findings show that the coronary and renal functions are particularly vulnerable in SHR during impaired nitric oxide synthesis, and that the end-organ damage is worsened by an increased intake of dietary salt. We suggest that dysfunction of the endothelium is the primary cause of the effects observed in this study.
在9周龄的自发性高血压大鼠（SHR）中研究了慢性抑制一氧化氮合成和饮食盐分的心血管效应。给接受低、中、高盐水平（分别为食物干重的0.2%、1.1%和6.0%的氯化钠）饮食的大鼠喂食Nω-硝基-L-精氨酸甲酯（L-NAME，食物中含0.025%，约20毫克/千克/天），持续3周。与未处理的SHR平均升高10至20毫米汞柱相比，L-NAME使所有处理组的收缩压升高了50至60毫米汞柱。高盐饮食并未进一步升高血压。L-NAME还诱导了心脏和肾脏肥大，而高盐饮食加剧了这些变化。此外，接受L-NAME处理的30只大鼠中有19只发生了中风，并且它们全部都有多处心肌梗死和肾脏损伤，而未接受L-NAME处理的大鼠没有中风、心肌或肾脏损伤的迹象。在实验结束时研究了体外肠系膜动脉环的反应。L-NAME处理组对去甲肾上腺素的血管收缩反应增强，对乙酰胆碱的舒张反应受到抑制。此外，单独的高盐饮食倾向于抑制对乙酰胆碱的反应。L-NAME处理使血浆肾素活性显著升高，而高盐饮食使其降低。L-NAME处理和高盐饮食均使24小时尿蛋白排泄增加。L-NAME和高盐饮食联合显著提高了血清肌酐浓度。我们的研究结果表明，在一氧化氮合成受损期间，SHR的冠状动脉和肾脏功能特别脆弱，并且饮食盐分摄入增加会加重终末器官损伤。我们认为内皮功能障碍是本研究中观察到的效应的主要原因。
