Deleterious effect in endothelin receptor–mediated coronary artery smooth muscle contractility in high-salt diet rats

High-salt diet has been suggested to increase the risk of heart disease. However, the mechanisms underlying coronary artery tension dysfunction caused by high-salt diet are unclear. Previous studies have shown that coronary artery spasm is often induced by endothelin-1 (ET-1) and thromboxane, leading to myocardial ischemia, while the store-operated Ca2+ entry (SOCE) function of coronary smooth muscle is very important in this process. Tension measurements of endothelium-denuded coronary artery ring segments showed that vasocontraction induced by U46619, ET-1, orSTIM1/Orai1-mediated SOCE was significantly lower in 4% high-salt diet rats than in control rats fed a regular diet. The results of western blotting and immunohistochemistry assays showed lower expression levels of endothelial receptors ETA and ETB, STIM1 and Orai1 in coronary artery of high-salt intake rats compared with control rats. Fibrosis was observed by using Masson's trichrome staining and picrosirius red staining. The plasma ET-1 concentration in high-salt diet rats was significantly higher than that of controls. The interventricular septum and posterior wall of high-salt diet rats were significantly thickened. Our findings indicated that coronary artery tension was significantly decreased in 4% high-salt diet rats and that this decrease may be due to the change of endothelin receptor and its downstream pathway SOCE related protein expression in coronary artery. Coronary fibrosis was observed in rats fed with high-salt diet. This study provides potential mechanistic insights into high-salt intake–induced heart disease. •Coronary vasoconstriction was weakened under high-salt diet condition.•The ETR-SOCE-mediated coronary contraction was decreased in high-salt diet rats.•Coronary fibrosis was observed in high-salt diet rats.•Serum ET-1 level was raised but ETR were decreased in Coronary after high-salt diet.