High fat plus high salt diet induced metabolic syndrome in wistar rat

220A

POSTERS: Obesity, Insulin Resistance, Diabetes

The study population consisted of 34 obese non-diabetic subjects (mean body mass index⫽39.03 kg/m2) with treated essential hypertension stage I to II (mean age⫽47 years, office BP⫽143/93 mmHg). All participants received orlistat 120 mg, three times per day, in combination with a 600 kcal deficient diet, for a period of 6 months. Office BP, weight, serum lipids, fasting glucose and urinary albumin excretion rate were followed. For the pooled population, at baseline, body weight was 112.4⫾17 kg, fasting glucose was 104.8⫾17 mg/dl, urinary albumin excretion rate was 105.3⫾66 mg/24h, serum cholesterol was 200⫾42 mg/dl, triglycerides were 124.5⫾64 mg/dl and low-density lipoprotein was 136.3⫾37 mg/dl. Regarding the echocardiographic data, left ventricular mass index was 116.4⫾36 g/m2, left atrial diameter was 3.7⫾0.5 cm and interventricular septum thickness was 1.15⫾0.19 cm. After 6 months, orlistat-treated subjects exhibited a significant decrease in office systolic BP, diastolic BP, pulse pressure, (⫺11.5⫾2.4 mmHg, ⫺6⫾1.92 mmHg and ⫺5.5⫾1.93 mmHg, respectively; p⬍0.05), heart rate (⫺3.1⫾1.2 beats/ min, p⬍0.05) and body mass index (⫺3.93⫾0.37kg/m2, p⬍0.001). Systolic BP fall was positively associated with left ventricular mass index (r⫽0.44, p⬍0.03), while BP decrease showed no correlation with weight reduction (p⫽NS). Furthermore, total cholesterol, low-density lipoprotein-cholesterol levels (⫺15.6⫾3.9 mg/dl and ⫺16.3⫾3.4 mg/dl, respectively; p⬍0.05), and urinary albumin excretion rate (⫺31⫾6.5 mg/dl, p⬍0.001), were notably attenuated. Orlistat treatment, plus hypocaloric diet, seems to improve BP control, independently of weight reduction, in obese hypertensive individuals. This could contribute to cardiovascular risk reduction, in this setting. Key Words: Essential Hypertension, Obesity, Orlistat

P-512 HEART RATE CONTROL IN HYPERTENSIVE SUBJECTS WITH TYPE 2 DIABETES MELLITUS Andris Vitols, Daina Voita, Mara Vitola, Vitolds Mackevics. Latvian Institute of Cardiology, Riga, Latvia; Riga Stradins University, Riga, Latvia. Symptomatic diabetic autonomic neuropathy is one of the disable disorders and may lead to sudden death. In order to recognize the early changes in cardiovascular neural control mechanisms before the appearance of clinical symptoms, non-invasive cardiovascular reflex tests are usually applied. However some modalities of tests have received substantial criticism. The objective in the present study was to assess the sensitivity of exercise induced heart rate (HR) and baroreceptor reflex (BR) chronotrope reaction as well as HR variability analysis for an early detection of autonomic nervous system impairment in type 2 diabetes mellitus (DM). On 15 essential hypertensive (EH) pts with type 2 DM (group A, 63 ⫾ 1.8 yr. aged men, HbA1C 10.1 ⫾ 0.9%), 17 EH pts without glucose metabolism disturbances (group B, gender and age matched) and 19 controls (C) at rest and during handgrip (with force 50% of maximal for 60s), beat-to-beat HR and finger mean arterial pressure (MAP) were monitored as well as bradycardic reaction to BR activation (by neck suction ⫺60 mmHg) was analysed. HR variability by time and frequency domain (applying fast Fourier transform) analysis of ECG 512 R-R interval files was estimated in supine and upright postures. Group A comparing to B and C was characterised by increased HR (80 ⫾ 2 vs.72 ⫾ 3 vs.70⫾ ⫾ 3 bpm; P⬍0.05) and decreased bradycardic reaction to BR activation (1.9 ⫾ 0.3 vs. 4.9 ⫾ 0.9 vs.10 ⫾ 0.6 bpm; P⬍0.05). At 60th sec of handgrip MAP increase was similar in all groups and HR increase was reduced in group A comparing to B and C (12 ⫾ 2 vs. 24 ⫾ 2 vs.18 ⫾ 2 bpm; P⬍0.05), but reaction to BR activation fully disappeared in group A and B, whereas in C remained 32 ⫾ 11% of resting value. At rest R-R interval variability in group A and B was diminished (P⬍0.01), but R-R interval decrease in upright position was less in group A than in group C (108 ⫾ 12 vs. 254 ⫾ 21 ms; P⬍0.05), whereas the difference of increase in low-high frequency band ratio (LF:HF) was not significant in group A and B. These results indicate that in hypertensive subjects with type 2 diabetes mellitus HR reaction to exercise and BR

AJH–May 2004 –VOL. 17, NO. 5, PART 2

activation has an advantage over HR variability analysis to ascertain an early impairment of autonomic control of sinus node. Key Words: Arterial Hypertension, Type 2 Diabetes Mellitus, Autonomic Dysfunction

P-513 HIGH FAT PLUS HIGH SALT DIET INDUCED METABOLIC SYNDROME IN WISTAR RAT Chengyi Shen, Zhiming Zhu, Zhencheng Yan, Yinxing Ni. Department of Hypertension and Endocrinology, Chongqing Hypertension Institute, Daping Hospital, Third Military Medical University, Chongqing, China. The metabolic syndrome (MS) is characterized by an association of insulin resistance, a tendency to abdominal obesity, a disturbance of lipid metabolism with elevated triglyceride and low HDL level, and commonly associated hypertension. It is well known that excess salt intake cause high blood pressure and extra fat administration led to obesity and insulin resistance. To understand the pathogenesis of MS, this study aims to establish an animal model that mimics MS in human. Sixty Wistar rats were divided into control groups with normal chow ( 7% fat and 0.5% salt ) and experimental groups with high fat ( 30%) plus high salt ( 4%). The weight gain, blood pressure, serum lipid, blood glucose and insulin resistance were examined. After rats were fed with normal chow and high fat plus high salt diet for 6 –7 months, intraperitioneal glucose tolerance test and extended hyperinsulinemic euglycemic clamp were performed on the rats of each group. Compared with normal control, rats with high fat plus high salt (HFS) developed severe visceral obesity [ body weight : 629 ⫾ 37 g vs. 453⫾36 g, P ⬍ 0.001 ; visceral fat weight : 56.8 ⫾ 7.4 g vs. 26.7 ⫾ 4.8 g, P ⬍ 0.001 ] and had higher serum levels of TG( 1.58⫾ 0.33vs.1.18⫾ 0.22 mmol/L, p ⬍ 0.01 ) and FFA(3.23⫾0.47 vs. 2.54⫾ 0.56 mmol/L, p⬍0.01). HFS rats had an obvious fasting hyperinsulinemia (42⫾6.8␮IU/ml vs 18 ⫾ 5.6 ␮IU/ml, P⬍0.01) but only marginal hyperglycemia (5.6⫾1.25 mmol/L vs. 4.9⫾1.14mmol/L, P⬍0.05) compared with rats with normal chow. Extended hyperinsulinemic euglycemic clamp showed that insulin sensitivity was 73% lower in HFS rats than normal diet rats (GIR: 8.3 ⫾ 0.46 mg. kg-1. min-1 vs. 2.2 ⫾ 0.34 mg. kg-1. min-1, P⬍0.01 ). A glucose intolerance was also observed in HFS, but not in control rats (2hPG: 8.0⫾1.75mmol/L vs. 5.6⫾1.56mmol/L, P⬍0.05). This study showed that long-term administration of high fat plus high salt diet caused clusters of abdominal obesity, dyslipidemia, insulin resistance and hypertension in Wistar rats. This rodent model mimics the basic characteristics of human MS and is helpful to understand the mechanism and therapy of MS. Key Words: Metabolic Syndrome, Rodent Model, Insulin Resistance

P-514 POLYMORPHISM OF PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR DELTA IN THE PATIENTS WITH METABOLIC SYNDROME Zhencheng Yan, Zhiming Zhu, Chengyi Shen, Yinxing Ni, Gang Zhang. Department of Hypertension and Endocrinology, Chongqing Hypertension Institute, Daping Hospital, Third Military Medical University, Chongqing, China. Peroxisome proliferator activated receptors (PPARs) play an important role in lipid metabolism and glucose homeostasis, however, PPAR delta is little known. Recent study showed that the variation at the PPAR delta locus associated with plasma LDL concentration in healthy men. The present study examines the polymorphism of PPAR delta in Chinese patients with metabolic syndrome (MS), type 2 diabetes mellitus (T2DM), and essential hypertension (EH). Polymerase chain reaction restricted fragments length polymorphism was used to study distribution of the PPAR delta 294T/C in exon 4 in 144 MS, 102 EH and 68 T2DM. Fasting insulin(FINS),fasting blood glucose(FBG), uric acid(UA),