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 normal salt (NS, 0.65% NaCl) diet for 2 weeks. There were three-fold increases in plasma Ang II, associated with a 60% reduction in flow-induced dilation (FID) in coronary arterioles of LS compared to NS dogs. In vessels of NS dogs, FID was primarily mediated by nitric oxide (NO), as indicated by an eliminated FID by 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 PDBu, an agonist of protein kinase C (PKC). The enhanced superoxide was normalized by apocynin, losartan (a blocker of AT1 receptor) and chelerythrine chloride (an antagonist of PKC). Western blotting indicated an upregulation of gp91phox and p47phox, 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 two weeks. There was a significant increase in plasma Ang-II in LS+Losa dogs, which however, was associated with normal FID and gp91phox 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.
- low-salt diet
- NAD(P)H oxide
- Copyright © 2010, American Journal of Physiology - Heart and Circulatory Physiology