Effects Of NNOS And CPT-I On The Contractility Induced By Palmitic Acid Of Myocardial Cells In Hypertensive Rats

Objective:To discuss whether ROS,nNOS,and CPT-I were involved in the regulation of PA on cardiac myocardial contractility in normal and hypertensive rats.Methods:The hypertensive rat model was prepared by injecting AngⅡ subcutaneously into rats by using a osmotic minipump.Sham-operated rats were underwent the same surgical procedure,but except for no pump insertion.Left ventricular myocytes were isolated enzymatically using the Langendorff perfusion system.Echocardiography was used to evaluate the cardiac function of rats.The blood pressure changes in rats were measured using the tail-cuff method.IonOptix system was used to measure the change in length of myocardial sarcomeres of left ventricular myocytes induced by electrical stimulation and the degree of contraction was observed;Western blot method was used to measure nNOS protein.Results:1.At the time of the study,the left ventricular structural parameters were not affected by Ang II,however,LVEF and LVFS were significantly decreased in hypertensive rats.There was no difference in diastolic parameters including E velocity and A velocity between the two groups.2.Left ventricular myocardial cells of Sham and Hypertension rats were incubated with superoxide scavenger(Tiron).After PA was given,the myocardial contractility was observed.It was found that Tiron did not affect the positive inotropic effect of PA in Sham rats(P=0.005,n=7),whereas there was no positive inotropic effect of PA in Hypertension rats(P=0.2,n=6).3.Immunoblotting showed that compared with Sham rats,nNOS activity in left ventricular myocardium of hypertension rats ’increased significantly.The nNOS activity in hypertension myocardial cells was inhibited by specific nNOS inhibitors(SMTC;L-VNIO).It was revealed that after treatment with nNOS inhibitors,the positive inotropic effect of PA in hypertension rat was restored(P=0.004,n=14;P<0.001,n=7).4.After pretreatment with CPT-I inhibitor(ETO,100μM,30min)and supplementation of PA,it was found that ETO inhibited the positive inotropic effect of PA on left ventricular myocytes in Sham-operated rats(P=0.74,n=14).Simultaneous administration of SMTC and ETO and supplementation of PA showed that SMTC+ETO could inhibit the positive inotropic effect of PA on left ventricular myocytes in hypertension group rats(P=0.49,n=8).Conclusions:1.The effect of palmitic acid on left ventricular cardiomyocytes is independent of ROS in healthy and hypertensive rats.2.The inhibitory effect of palmitic acid on myocardial contractility may be related to the increased nNOS and protein CPT-I in hypertension rats myocardial cells.