Perindopril improves angiogenesis in myocardium of obese zucker rats

AJH–May 2003–VOL. 16, NO. 5, PART 2

P-533 METABOLIC SYNDROME IN HYPERTENSIVE PATIENTS WITH LEFT VENTRICULAR HYPERTROPHY Ivan S Tasic, Branko K Lovic, Vladisav Stefanovic, Dragan Djordjevic, Stevan Ilic, Natasa L Miladinovic. Cardiology, Institute for cardiology and rheumatology Niska Banja, Niska Banja, Serbia, Yugoslavia; Nephrology, Institute for nephrology and hemodialysis, Nis, Serbia, Yugoslavia; Microbiology, Institute for microbiology and immunology, Nis, Serbia, Yugoslavia. Metabolic syndrome (MS) carries of a number of risk factors for some patients with cardiovascular (CV) diseases. These risk factors, including isulin resistence, dyslipidermia, hypertension and obesity, increase the risk of the development of DM and multiply the risk of CV diseases. Aim: To prove the presence of MS in patients with hypertension and LVH analysing clinical parametres and to estimate the impact of this syndrome on patient prognosis. Methods: There have been analysed 73 hypertensive patients (43 male patients), avarage age 56.3 ⫾ 8.5 with echo proved LVH (avarage LV mass index 163.5 ⫾ 31,8 g/m2). Every patient has got the following results echo, ECG, treadmill exercise testing, 24-hour AMBP and 24hour Holter monitoring (analysis of ventricular arrhythmias-VA and heart rate variablility - HRV). MS is defined according to NCEP ATP III. Results: 36 patients (55 ⫾ 8 years) fulfilled the criterion of MS. They had significantly higher glucose level (5.9 ⫾ 1 vs 5.1 ⫾ 0.6. p⬍0.001), lower HDL cholesterol 0.99 ⫾ 0.3 vs 1.2 ⫾ 0.3, p⬍0.009), higher triglycerides (2.8 ⫾ 2 vs. 1.6 ⫾ 0.6, p⬍0.02) and higher BMI (29.6 ⫾ 3.8 vs. 27.8 ⫾ 3, p⬍0.03). LV mass index was also higher in these patients but not statistically significant ( 165. 5 ⫾ 29 vs. 159.9 ⫾ 34, ns.) This group of patients had more frequent complex VA (19 to 6, p⬍0.001) and significantly lower values of HRV (SDNN – 114.1 ⫾ 25 vs. 126.4 ⫾ 21, p⬍0.05; RR interval – 809.6 ⫾ 113 vs. 885.7 ⫾ 115, p⬍0.02). After 12 month treatment this group of patients had significantly higher glucose level (5.7⫾ 1.4 vs. 5 ⫾ 0.7, p⬍0.03), higher double product at physical exercise test (28 ⫾ 5 vs. 25 ⫾ 4, p⬍0.03), lower day SDNN (103.4 ⫾ 27 vs. 116.4 ⫾ 21, p⬍0.05) shorter day and night RR interval (802.4 ⫾ 132 vs. 894 ⫾ 131, p⬍0.007; 918 ⫾ 138 vs. 1026.5 ⫾ 131, p⬍0.04). Significant ST depression has been registered in 8 patients of this group in contrast to 4 patients in the group without metabolic syndrome (ns). After 4 year observation 5 patients in this group had serious cardiovascular incidents (3 CVI – 1 death, 2 IM) while in the second group 2 patients (1 IM and 1 PTCA with inbuilt stent)(ns). Conclusion: MS in hypertensive patients with LVH is connected with significantly higher activity of sympathetic nervous system and increased risk of CV incidents. Key Words: left ventricular hypertrophy, metabolic syndrom, heart rate variability

P-534 PERINDOPRIL IMPROVES ANGIOGENESIS IN MYOCARDIUM OF OBESE ZUCKER RATS Jorge E. Toblli, Gabriel Cao, Graciela DeRosa, Pedro Forcada. Laboratory of Experimental Medicine, Hospital Aleman, Buenos Aires, Argentina. Diabetes and hypertension are associated with vascular rarefaction in various tissues. Vascular endothelial growth factor (VEGF) is a potent angiogenic factor throughout NO production. Additionally, ACE inhibitors have demonstrated some angiogenic effect. Our objective was to study possible angiogenic effect of perindopril (P) on VEGF in myocardium of obese Zucker rats (OZR), which is a well-known animal model of human syndrome X, and lean Zucker rats (LZR) as control. G1 OZR (n⫽10); G2 OZR⫹P(n⫽10); G3 LZR(n⫽10). G2 with P 3mg/kg/day for 6 months. Hearts were processed for high-resolution light microscopy (HRLM), immunohistochemistry with monoclonal anti-VEGF. The nu-

POSTERS: Obesity, Insulin Resistance, Diabetes

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merical density of myocytes and coronary capillaries was determined by counting the total number of myocytes and vessels £ 8 m. We evaluated: 1-myocyte diameter (Md); 2-density of myocytes/area (Dm); 3-density of capillaries/area (Dc), 4-Dm /Dc ratio; and 5- % VEGF /area. At the end of the experiment (6th month): Systolic Blood Pressure mmHg (G1: 152.4* ⫾ 3; G2: 127 ⫾ 3.2; G3 124.2 ⫾ 1.7). Md (m) (G1: 32.7 ⫾ 2.6*; G2: 21.2 ⫾ 1; G3: 20.9 ⫾ 2.1). Dm (G1: 19.6 ⫾ 2.1*; G2: 47.3 ⫾ 1.5; G3: 47 ⫾ 1.1). Dc (G1: 10.1 ⫾ 1.7*; G2:31.2 ⫾ 2.7 G3: 31.4 ⫾ 3.1). Dm/Dc ratio (G1: 2 ⫾ 0.4*; G2: 1.5 ⫾ 0.1; G3: 1.5 ⫾ 0.1). % VEGF (G1: 1.04 ⫾ 0.03*; G2: 7.45 ⫾ 2.45; G3: 2.29 ⫾ 0.43).*p⬍.01 vs.G2 y G3. Positive correlation (p⬍.01) was observed between % VEGF and Dc in all groups. G2 (OZR⫹P) showed lower Md; higher Dc, Dm and % VEGF with better Dm/Dc ratio than OZR (G1). On the other hand, OZR (G1) presented vascular rarefaction associated with a decrease in VEGF in myocardium. P seems to restore this situation by increase VEGF and, therefore, improve angiogenesis in this animal model. Key Words: Angiogenesis, ACE inhibitors, Obese Zucker Rats

P-535 VASODILATATION FUNCTION IN ELDER HYPERTENSIVES WITH AND WITHOUT DIABETES MELLITUS Liangdi Xie, Yuerong Yan, Penghong Li, Xin Wu. Department of Cardiology, First Affiliated Hospital, Fujian Medical College,Fujian Hypertension Research Institute, Fuzhou, Fujian, China; Department of Cardiology, Fujian Geriatric Hospital, Fuzhou, Fujian, China. To explore the vasodilatation function changes in elder hypertnsives with (HT⫹DM) and without (HT) diabetes mellitus. 61 elder patients was entered into 3 groups: Hypertensives (HT , n⫽23) , Hypertensives with diabetes (HT⫹DM, n⫽23), and normotensives without diabetes(NT, n⫽15). Endothelium dependent vasodilatation and non-endothelium dependent vasodilatation function was determined using high resolution B mode sonography technique. Plasma endothelin level was determined using enzyme labeled immunoassay. It was found that endothelium dependent vasodilatation was significantly different among HT⫹DM , HT and NT patients ( HT⫹DM: 4.54 %⫾2.51 % , HT:7.51 % ⫾3.20 %, vs NT:15.67 %⫾5.76% , P ⬍ 0.01 respectively). Marked deterioration of vasodilatation function was found in HT⫹DM than in HT patients P ⫽ 0.029). There was no significant difference of non- endothelium dependent vasodilatation function among HT⫹DM , HT and NT patients (P ⬎ 0.05). Linear regression analysis shown that there was a close correlation between endothelium dependent vasodilatation function and plasma glucose, ET-1 and SBP (P ⬍ 0.01 respectively. Multiple stepwise regression analysis showed that systolic blood pressure was an only independent factor for brachial vasodilatation function (R2 ⫽ 0.397, df ⫽ 60, P ⬍ 0.01), and ET-1 was an only independent factor for fasting plasma glucose (R2 ⫽ 0.145, df ⫽ 60, P ⫽ 0.02). It is thus concluded that hypertension per se is an independent risk factor for vascular endothelial function damage in elder hypertensives. Diabetes mellitus aggravated the deterioration of vascular endothelial function in hypertensives. Key Words: Diabetes Mellitus, Endothelium dependent relaxation function, Hypertension

P-536 ROLE OF SOLUBLE ADHESION MOLECULES IN THE PATHOGENESIS OF HYPERTENSIVE VASCULAR LESIONS IN OBESITY Minoru Yamakado, Yuko Ishizaka, Eiko Takahashi, Toshio Nakadate. Department of Health Care, Mitsui Memorial Hospital, 1 Kanda Izumicho, Chiyoda-ku, Tokyo, Japan; Depatment of Hygiene and Preventive Medicine, Showa University, School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, Japan. Monocyte adhesion on vascular endothelium by adhesion molecules is the first step for not only atherosclerosis but also hypertensive vascular