Effect Of Antihypertensive Drugs On Myocardial Fibrosis And Insulin Resistance In Hypertensive Patients

Background and objective : Left ventricular hypertrophy(LVH), a common complication of essential hypertension, consisted of cardiomyocytes hypertrophy and an exaggerated accumulation of myocardium collagen. Renin-angiotensin-aldosterone system played an important role in LVH. The concentrations of serum matrix metalloproteinase - 1 ( MMP-1 ) and N-terminal propeptide of type procollagen( P NP) were determined before and after antihypertensive therapy in hypertensive patients. The results of insulin resistance of hypertensive patients were observed. The objective of the present study is to view the influence of chronic drug therapy on accumulation of myocardium collagen and insulin resistance in hypertensive patients.Methods: one hundred and thirty-one hypertensive patients with age of 52.1 7.9 years and thirty-nine health control with age of 53.4 7.6 years were enrolled, including sixty-eight men and one hundred and two women. Blood pressure (BP), heart rate (HR), body mass index (BMI) and waist/hip ratio (WHR) were measured. Patients were assigned to fufangjiangyapian, fosinopril, fosinopril+ indapamide three group antihypertensive drugs after randomization. This follow up study continued for 12-16 months. Oral glucose tolerance test (OGTT) and insulin releasing test were performed at baseline and after the observation. Serum matrix metalloproteinase-1 concentration wasdetermined by enzyme-linked immuno-sorbent assay (ELISA), and serum N-terminal propeptide of type procollagen concentration was determined by specific radioimmunoassay. Insulin sensitivity index was calculated with Cederholm formula and P-cell secretory function was indicated by . All statistical analyses were made on computer by the SPSS 11.5 soft package.Results: MMP-1 of hypertensive patients before remedy differed greatly from that of health control (5.349 +4.167ng/ml verses 6.398 +3.548ng/ml, /K0.05). PIUNP of hypertensive patients before therapy differed greatly from that of health control (3.666 + 1.372 ug/L verses 2.653 + 1.071 ug/L, /K0.01). Neither MMP-1 or PIHNP changed significantly in fosinopril-treated patients. In fosinopril+indapamide-treated patients, the concentration of MMP-1 increased significantly ( from 4.032+3.038ng/ml to 6.586+3.790ng/ml, p=0.002 ), the concentration of PHINP decreased significantly( from 3.637+1.139g/L to 3.056+1.112g/L, p=0.036 ) . In Mangjiangyapian-treated patients, the concentration of MMP-1 increased significantly ( from 4.866+3.763ng/ml to 7.366+4.409ng/ml, p=0.001 ), the concentration of PHINP decreased significantly ( from 4.071+ 1.133 ug/L to 3.294+1.404g/L,p=0.001 ) . Insulin sensitivity index (ISI) and of patients with essential hypertension before therapy decreased significantly with that of health control. ISI and increased in both of fosinopril and fufangjiangyapian treatment patients.Conclusion: The present study suggested that the efficacy of chronic combined therapy with fosinopril+indapamide and fufangjiangyapian in lowering blood pressure of hypertensive patients was superior to fosinopril monotherapy. The efficients of prohibition accumulation of myocardium collagen with fosinopril+indapamide and fufangjiangyapian was superior to fosinopril monotherapy. MMP-1 and PNP could be used to assess the ability of antihypertensive treatment to regress myocardial fibrosis inhypertensive patients without renal and hepatic diseases. Chronic fosinopril monotherapy and fufangjiangyapian can improve IR and metabolism of blood glucose in hypertensive patients.