Serial Observation On The Myocardium And Plasma Level Of ADM And ANP In STZ-induced Diabetic Rats And The Effect Of Enalapril Treatment

Diabetic cardiomyopathy (DMC) is a common complication of diabetes characterized by high incidence of congestive heart failure. Mechanisms underlying multifactor-mediated development and progression of DMC is incompletely understood. Many pathological processes, including abnormal energy metabolism , microvascular lesions, myocardial and interstitial fibrosis,cardial autonomic neuropathy, oxidative stress, and apoptosis,may be involved in the pathogenesis of DMC.Recently, it is emphasized that over activation of renin-angiotensin system(RAS) and interaction of vasoactive peptides may play an important role in the development of DMC.Study shows excessive production of angiotensin Ⅱ(AgⅡ) can induce DMC and treatment by angiotensin converting enzyme inhibitor(ACEI) and angiotensin Ⅱ receptor blocker(ARB) can improve heart function of diabetics. Adrenomedullin(ADM) and atrial natriuretic peptide(ANP) ,two potential vasodilative peptides , have many biological functions such as vasodilation,blood pressure lowering and diuresis. Changes in local and circulation concentrations of ADM and ANP are associated with pathophysiology of cardiovascular diseases. Plasma ADM and ANP levels increase in congestive heart failure(CHF), in parallel to the desease severity, and effective management to CHF can decrease their levels. In spite of the undefined relationship between ADM or ANP and diabetes, patients with diabetic retinopathy(DR) and/or diabetic nephropathy(DN) have significantly higher plasma concentrations of ADM and ANP as compared to control,suggesting that ADM and ANP are related to diabetic microangiopathy.However,investigation on DMC remains rare.ObjectThe present study was aimed to observe the serial alteration in ADM and ANP levels of myocardium and plasma in the development and progression of DMC and the effect of enalapril treatment on two peptides in STZ-induced diabetic rats, exploring the association of ADM or ANP with DMC. Design and methodsFifty-two adult male Wistar rats were allocated randomly into three groups: 1-month group and 3-month group both included control and diabetic rats; 5-month group included control, diabetic rats and enalapril treated diabetic rats( 2mg.kg"1.d"1orally from 1st to 5th month of duration). Streptozotocin(STZ) was used to induce experimental diabetes by a intraperitoneal(ip) injection. Metabolism cage was adopted to collected nocturia of twelve hours at scheduled duration and urine protein excretion rate(UPE) was determined with chemically colorimetric method. Determination of plasma ADM and ANP concentrations was performed with radioimmunoassay. Heart weight index(the ratio of heart weight to body weight) was recorded when experimental animals were sacrificed. Left ventricular tissues for electron microscopy scanning and in situ hybridization(ISH) analysis were sampled from respective one of the control and diabetic rats of scheduled duration(l,3,5month). Semiquantitative reverse-transcription polymerase chain reaction(RT-PCR) was applied to evaluate the messenger RNA(mRNA) contents of ADM and ANP in both left and right ventricles of diabetic rats at 1 and 5-month duration. ResultsExperimental animals manifested persistent hyperglycemia accompanied by polyuria, polydipsia and loss of body weight after STZ administration. Blood glucose concentrations at each scheduled end-point in diabetic rats were significantly higher than that in control. HWI of diabetic rats at 1,3,5 month duration present a significant increase(0.452 + 0.170 vs0.304±0.037, 0.431+0.140 t?0.312±0.025, 0.439 + 0.100 w 0.308+ 0.039,respectively. 0.05).As compared to diabetic rats,enalapril-treated subgroup got a decrease in UPE at 5-month (252.3 + 68.4 w 399.5+ 134.5, 0.05) .Enalapril-intervented subgroup got a prominent elevationin plasma ADM level (22.45 ± 13.77 vs 10.41+3.97,