The Role And Mechanism Of Interaction Between Parathyroid Hormone And Salt In Left Ventricular Hypertrophy

Background High salt intake can increase urinary calcium excretion in the kidney,which stimulates the synthesis and release of PTH.Left ventricular hypertrophy is a change of ventricular wall thickening,heart weight increase,and myocardial remodeling.Left ventricular hypertrophy is an independent risk factor for heart failure.Previous studies have found that high salt intake and hyperparathyroidism can lead to left ventricular hypertrophy,but it is not clear whether the interaction between them affects the incidence of left ventricular hypertrophy.An in-depth study of the effects of salt intake,PTH intervention,and their interaction on left ventricular hypertrophy can provide a new target for preventing and treating heart failure.Objective To clarify the role and possible mechanism of interaction between PTH and salt in left ventricular hypertrophy and to determine whether captopril intervention can block the effects of sustained stimulation of PTH and excessive salt intake on left ventricular hypertrophy.Methods(1)Forty 8-week-old male Sprague Dawley rats were randomly divided into 8 groups:sham operation group,PTH group,low salt group(0.6%Na Cl),high salt group(8%Na Cl),PTH+low salt group(0.6%Na Cl),PTH+high salt group(8%Na Cl),PTH+low salt(0.6%Na Cl)+captopril group,PTH+high salt(8%Na Cl)+captopril group,with5 rats in each group.The feeding environment is consistent,free to eat and drink.All operations are in line with the "3R" principle.(2)Surgical implantation capsule osmotic pump: all groups that needed PTH intervention were continuously pumped with rat recombinant PTH(1-34)(2pmol/kg.h)for two weeks;the sham operation group,the low salt group,and the high salt group were continuously pumped with sterilized water for injection for two weeks.Intragastric gavage: the sham operation group and the PTH group were given intragastric gavage with sterilized water for injection,and the other groups were given different concentrations of normal saline(10-20ml/kg/d)and captopril(10mg/kg/d)for two weeks by gavage.(3)A non-invasive blood pressure measurement system measured the blood pressure of the rat caudal artery.An electronic balance scale was used to measure the heart weight and body weight,and the heart mass index was calculated.The thickness of the left ventricle posterior wall was measured by a vernier caliper.Hematoxylineosin staining showed the morphological changes of myocardial tissue.The relative expression of type III collagen was determined by immunohistochemistry.Results(1)The effect of PTH and salt intake on blood pressure of rats: the blood pressure of all rats treated with PTH and high salt was significantly higher than that before the intervention,and also significantly higher than that without the intervention(P<0.05).There was no significant change in blood pressure after PTH or high salt intervention alone.Captopril intervention could significantly decrease the blood pressure of rats with PTH combined with high salt(P<0.05).(2)The effects of PTH and salt intake of different concentrations on HW,HMI,and LVPWT of rats: the heart weight of rats in the PTH+high salt group was significantly heavier than that in sham operation group,PTH group,low salt group,and high salt group(P<0.05);the heart mass index of PTH+high salt group was significantly higher than that of PTH group and low salt group(P<0.05).Compared with the sham operation and low salt groups,the left ventricular posterior wall thickness of the PTH+high salt group was significantly thickened(P<0.05).However,captopril intervention temporarily failed to reverse the changes in heart weight,heart mass index,and left ventricular posterior wall thickness caused by high concentration PTH and different salt concentrations.(3)The effects of PTH and salt intake at different concentrations on the histological morphology of the myocardium in rats: the myocardium cells in the sham operation group were arranged neatly,with uniform cell size,clear nuclear and cytoplasmic structure,and no degeneration or necrosis of the myocardium,and no infiltration of inflammatory cells in the interstitium;compared with the other groups,the myocardial cells in the PTH+high salt group were significantly hypertrophy and disordered,with some myocardial cells dissolved and necrotic,accompanied by a large number of inflammatory cells infiltration.In the PTH+low salt group,only mild hypertrophy and slightly disordered arrangement of cardiomyocytes were observed,and no lytic necrosis or infiltration of inflammatory cells was observed.Captopril intervention can improve the pathological changes of myocardial tissue caused by PTH and salt intake in different concentrations.(4)The effects of PTH and salt intake at different concentrations on the expression of type III collagen,a marker of myocardial fibrosis in rats: compared with the sham operation group,the expression of type III collagen in all groups except the low salt group was significantly increased(P<0.05);the expression of type III collagen in the myocardium of rats treated with PTH and high salt was significantly higher than that in the other groups(P<0.05).After captopril intervention,the expression of type III collagen in rat myocardium was significantly reduced by PTH and salt intake at different concentrations(P<0.05).Conclusions In Sprague Dawley rats,PTH combined with high salt increased blood pressure,heart weight,cardiomyocyte hypertrophy,left ventricular hypertrophy,and myocardial fibrosis.Captopril intervention can reduce blood pressure,pathological changes of myocardial tissue and myocardial fibrosis,but can not completely reverse left ventricular hypertrophy.