Department of Physiology, New York Medical College, Valhalla, New York 10595, USA.
Am J Physiol Heart Circ Physiol. 2010 Nov;299(5):H1476-83. doi: 10.1152/ajpheart.01250.2009. Epub 2010 Sep 10.
Low-salt (LS) diet has been considered to be beneficial in the prevention and treatment of hypertension; however, it also increases plasma angiotensin (ANG) II and may cause adverse cardiovascular effects, such as endothelial dysfunction. We assessed endothelial function of coronary arterioles and vascular superoxide production, as a function of LS diet. Dogs were fed with LS (0.05% NaCl) or a normal-salt (NS, 0.65% NaCl) diet for 2 wk. There were threefold increases in plasma ANG II, associated with a 60% reduction in flow-induced dilation (FID) in coronary arterioles of LS compared with NS dogs. In vessels of NS dogs, FID was primarily mediated by nitric oxide (NO), as indicated by an eliminated FID by N(ω)-nitro-l-arginine methyl ester (l-NAME). In vessels of LS dogs, however, FID was eliminated. Administration of apocynin, a NAD(P)H oxidase inhibitor, partially restored FID and additional l-NAME eliminated FID. Generation of superoxide, measured with dihydroethidium, was significantly greater in vessels of LS than in NS dogs, which was further increased in response to ANG II or phorbol 12,13-dibutyrate, an agonist of protein kinase C (PKC). The enhanced superoxide was normalized by apocynin, losartan (a blocker of angiotensin type 1 receptor), and chelerythrine chloride (an antagonist of PKC). Western blotting indicated an upregulation of gp91(phox) and p47(phox), associated with increased expression of phosphorylated PKC in vessels of LS dogs. In separate experiments, dogs were fed simultaneously with LS and losartan (LS + Losa) for 2 wk. There was a significant increase in plasma ANG II in LS + Losa dogs, which, however, was associated with normal FID and gp91(phox) expression in coronary arterioles. In conclusion, LS led to endothelial dysfunction, as indicated by an impaired flow-induced dilation caused by decreasing NO bioavailibility, a response that involves angiotensin-induced activation of PKC that, in turn, activates vascular NAD(P)H oxidase to produce superoxide.
低盐（LS）饮食已被认为有益于高血压的预防和治疗；然而，它也会增加血浆血管紧张素（ANG）II，并可能导致不良的心血管效应，如内皮功能障碍。我们评估了 LS 饮食对冠状动脉小动脉内皮功能和血管超氧化物产生的影响。狗被喂食 LS（0.05%NaCl）或 NS（0.65%NaCl）饮食 2 周。与 NS 狗相比，LS 狗的血浆 ANG II 增加了三倍，导致冠状动脉小动脉的血流诱导扩张（FID）减少了 60%。在 NS 狗的血管中，FID 主要由一氧化氮（NO）介导，这表明 N（ω）-硝基-L-精氨酸甲酯（l-NAME）消除了 FID。然而，在 LS 狗的血管中，FID 被消除了。烟酰胺腺嘌呤二核苷酸（NAD（P）H）氧化酶抑制剂 apocynin 的给药部分恢复了 FID，并且额外的 l-NAME 消除了 FID。用二氢乙啶测量的超氧化物的产生在 LS 狗的血管中明显大于 NS 狗，并且对 ANG II 或佛波醇 12,13-二丁酸（蛋白激酶 C（PKC）的激动剂）的反应进一步增加。apocynin、losartan（血管紧张素 1 型受体阻滞剂）和 chelerythrine chloride（PKC 拮抗剂）使增强的超氧化物正常化。Western blotting 表明 LS 狗的血管中 gp91（phox）和 p47（phox）上调，与磷酸化 PKC 的表达增加相关。在单独的实验中，狗同时喂食 LS 和 losartan（LS + Losa）2 周。LS + Losa 狗的血浆 ANG II 显著增加，但在冠状动脉小动脉中，FID 和 gp91（phox）的表达正常。总之，LS 导致内皮功能障碍，表现为由于 NO 生物利用度降低导致的血流诱导扩张受损，这一反应涉及血管紧张素诱导的 PKC 激活，反过来激活血管 NAD（P）H 氧化酶产生超氧化物。
