Obesity does not increase sympathetic vascular tone in hypertensives

AJH–May 2005–VOL. 18, NO. 5, PART 2

Both group reduced MA, but differences in prevalence of positive MA between MS and non-MS patients remained significant (24.5% vs. 10.1%,respectively). Prescription of ACEi and ARBs was similar in both groups (74.9% in SM, vs. 70.1% in non-MS, P⫽NS). In conclusion, our usual hypertension care allowed to reach similar BP and LDL-cholesterol goals, both in MS and non-MS patients. However, it seem that global cardiovascular risk could remain higher in treated hypertensive with MS as suggested by 3 fold higher incidence of new onset diabetes and double prevalence of positive MA. The convenience of lower therapeutical goals in hypertensive patients with MS should be forward evaluated. Key Words: Metabolic Syndrome, Microalbuminuria, Therapeutical Goals

P-516 GENE EXPRESSION PROFILE IN INSULIN-SENSITIVE TISSUE IN RATS WITH METABOLIC SYNDROME Tingbing Cao, Hai Nie, Zhencheng Yan, Jian Zhong, Zhiming Zhu. Department of Hypertension and Endocrinology, Center for Hypertension and Metabolic Disease, Chongqing Hypertension Institute, Daping Hospital, Third Military Medical University, Chongqing, China. High fat intake and less physical activity are high risk environmental factors for metabolic syndrome (MS). This study investigated the effects of high fat diet and exercise on gene expression profiles associated with the nuclear receptors, glucose and lipid metabolism, inflammation and energy in insulin-sensitive tissues in MS rats. Methods: MS rat model was induced by high fat diet and salt, which was accorded to our previous work. Wistar rats were divided into the normal diet control (NC), high-fat and salt diet (MS), normal diet with exercise (NCE) and MS with exercise (MSE). The regular exercise means that rats swim three times (1hr/time) weekly and last for 48 weeks. Gene expression profiles were measured using RT-PCR in insulin-sensitive tissue after rats were decapitated. Results: (1) skeletal muscles tissues: compared with NC rats, 4 gene (CRP, UCP1, SCD1 and SCD2) expressions were reduced and 9 gene(MCP1, IL-6, UCP1, UCP2, M-CPT1, LACS, PDK4, FABP3, P22Phox)expressions increased in MS rats.In NCE rats, 5 gene (MCP1, UCP3, PDK4, SCD1 and SCD3) expressions were up-regulated, whereas 7 gene (IL-6, SOCS3, UCP1, UCP3, FABP3, ABCA1, P22-Phox) expressions down-regulated. In MSE rats 4 gene (CRP, UCP1, SCD1 and SCD2) expressions were up-regulated and 9 gene (MCP1, IL-6, UCP3, M-CPT1, LACS, CD36, ADRP, PDK4, FABP3) expressions downregulated compared with NC rats.(2)visceral fat tissues: compared with NC rats, 2 gene (CRP and IL-6) expressions increased and other 18 gene expressions reduced in MS rats. In NCE rat, 3 gene (UCP1, UCP2, P22-Phox) expressions were up-regulated whereas 12 gene expressions were down-regulated; In MSE, 2 gene(CRP and PPAR-beta) expressions were increased and 10 gene expressions reduced. (3) brown fat tissues: compared with NC rats, 2 gene(CRP and FABP3) expressions were up-regulated, but 3 gene (IL-6, SOCS3 and ABCA1) expressions reduced in MS rats. Conclusions: High fat and salt intake and exercise had a significant effect on the multiply gene expression in the insulin-sensitive tissue. Further work need to link these gene changes with the pathogenesis of MS ( Supported by NSFC grant 30470830). Key Words: Gene, Metabolic Syndrome, Risk Factors

POSTERS: Metabolic Syndrome

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P-517 INCREASED DIETARY SODIUM PARTIALLY BLUNTS THE AMELIORATION OF INSULIN RESISTANCE INDUCED BY DIETARY POTASSIUM SUPPLEMENTATION IN A NEUROENDOCRINE MODEL OF VISCERAL OBESITY Mario LR Cesaretti, Milton Ginoza, Maria T Zanella, Artur B Ribeiro, Osvaldo Kohlmann. Nephrology-Hypertension Division, Federal University of Sa˜o Paulo, Sa˜o Paulo, Sa˜o Paulo, Brazil. Previous studies from our laboratory showed that dietary potassium supplementation improves insulin sensitivity and reduces blood pressure in the spontaneously hypertensive rats; Objectives: The aim of this study was to evaluate the effects of increased contents of potassium alone or potassium ⫹ sodium chloride in the diet upon tail arterial pressure (TAP) and glucose metabolism of Wistar rats with visceral obesity induced by neonatal administration of MSG (2 mg/day/SC from day 1t o11th after birth), a model with insulin resistance. Methods: MSG (2 mg/kg/day) was administered to newborn Wistar rats during the first 11 days of life. At 3 months of age they were separated into 3 groups and were feed for 12 weeks with: group1-regular rat chow ⫹ tap water to drink (MSG, n⫽ 13); group 2-potassium enriched diet (K⫹ content: 3 times standard chow) ⫹ tap water to drink ((MSG-K⫹, n⫽12) and group 3 same diet of group 2 but receiving 1% saline to drink instead tap water (MSG⫹K⫹Na, n⫽12). Rats receiving vehicle instead MSG injections at neonatal period and feed with regular rat chow (C, n⫽ 12) or potassium enriched chow (C⫹K, n⫽ 10) and tap water to drink were used as controls. At the end of the follow-up period an oral glucose tolerance test (OGTT, glucose overload: 68 mg/kg) was performed in all animals. Areas under the curves of glucose (AUCG, mg/dl) and insulin (AUCI, mU/l) and the insulin sensitivity index (ISI mg僒1mU僒1) were determined. Upon animals sacrifice the left ventricle was weighted. Results: * p⬍0.05 vs C , ⫹ p ⬍0.05 vs MSG (see table) Conclusion: Dietary potassium supplementation decreases blood pressure and improves glucose metabolism of MSG-induced visceral obese rats, and this effect is partially blunted by dietary sodium overload. Improvement in the insulin sensitivity may account for the effects of dietary potassium supplementation on blood pressure.

C C⫹K MSG MSG ⫹ K MSG ⫹ K ⫹ Na

TAP 12th week

ASCG

ASCI

ISI

115.0 ⫾ 1.52 107.7 ⫾ 1.67* 112.15 ⫾ 2.51 105.6 ⫾ 2.14† 104.5 ⫾ 4.02

136.96 ⫾ 12.38 123.92 ⫾ 6.42 192.54 ⫾ 9.96* 134.66 ⫾ 4.12† 176.84 ⫾ 13.14

3.41 ⫾ 0.17 4.16 ⫾ 0.23 4.78 ⫾ 0.71 2.90 ⫾ 0.11† 3.00 ⫾ 0.14†

28.38 ⫾ 1.98 20.34 ⫾ 1.26 4.89 ⫾ 0.66* 27.49 ⫾ 1.84† 21.69 ⫾ 2.25†

Key Words: Insulin Resistance, Neuroendocrine Obesity, Potassium

P-518 OBESITY DOES NOT INCREASE SYMPATHETIC VASCULAR TONE IN HYPERTENSIVES Marcelo LG Correia, Alexei V Agapitov, Christine A Sinkey, Allyn L Mark, William G Haynes. General Clinical Research Center and Department of Internal Medicine, University of Iowa, Iowa City, IA. Skeletal muscle sympathetic nerve activity (MSNA) is increased in obesity and hypertension and may increase sympathetically mediated vascular tone. We tested the hypothesis that elevated MSNA in obese hypertensives is associated with increased sympathetically mediated vascular tone. Forearm vascular resistance (FVR) was calculated from plethysmographic blood flows. Sympathetic vascular tone was assessed

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POSTERS: Metabolic Syndrome

AJH–May 2005–VOL. 18, NO. 5, PART 2

by FVR responses before and after intra-arterial phentolamine (120␮g/ min). Four groups were studied: obese (n⫽25, age⫽39⫾2, BMI⫽35⫾1, MAP⫽88⫾2) and lean (n⫽25, age⫽39⫾2, BMI⫽22⫾1, MAP⫽87⫾2) normotensives, and obese (n⫽12, age⫽47⫾2, BMI⫽38⫾2, MAP⫽100⫾3) and lean (n⫽12, age⫽48⫾3, BMI⫽25⫾1, MAP⫽100⫾2) hypertensives. Phentolamine completely blocked vasoconstriction to norepinephrine (480pmol/min) indicating complete alphaadrenergic inhibition. MSNA measured by fibular microneurography was higher in obese than lean normotensives but similar in obese and lean hypertensives (Table). Reductions in FVR induced by phentolamine were similar in obese and lean normotensives but greater in lean than obese hypertensives (Table). In summary, our data show that sympathetically mediated vascular tone is not augmented in obese hypertensives despite elevated MSNA. Furthermore, lean hypertensives appear to have higher alpha-adrenergic vascular tone for the same level of MSNA than obese hypertensives. Our results suggest that obesity may blunt the vasoconstrictor effect of elevated MSNA in hypertension. MSNA and ⌬FVR in obese and lean normotensives and hypertensives MSNA-NTN ⌬FVR-NTN MSNA-HTN ⌬FVR-HTN

Obese

Lean

P Value

31 ⫾ 3 bpm ⫺57 ⫾ 2% 37 ⫾ 4 bpm ⫺50 ⫾ 6%

22 ⫾ 1 bpm ⫺57 ⫾ 3% 36 ⫾ 4 bpm ⫺63 ⫾ 3%

.01 .93 .98 .05

NTN ⫽ normotensives; HTN ⫽ hypertensives; bpm ⫽ bursts/min

Key Words: Obesity Hypertension, Sympathetic Activity, Vascular Tone

P-519 PREVALENCE AND CLINICAL CHARACTERISTICS OF METABOLIC SYNDROME IN THE SPANISH HYPERTENSIVE POPULATION Alejandro De la Sierra, Ramon Romero, Josep Bonet, Montserrat Perez, Juan Salvador Lopez, Maria Teresa Antonio, Maria Teresa Aguilera, Jose Maria Taboada. Internal Medicine, Hospital Clinic, Barcelona, Spain; Nephrology, Hospital Germans Trias i Pujol, Badalona, Spain; Pharma Research, Pharma Consult Services. S.A., Barcelona, Spain; Medical Department, Sanofi-Aventis Group, Barcelona, Spain. The aim of the present study was to assess the prevalence and clinical characteristics of metabolic syndrome (MS) in the hypertensive population. The present is a cross-sectional epidemiological study in a sample of 19,039 hypertensive patients attended in primary care centres. MS was defined using the NECP (ATP-III) criteria. We found that 8488 patients (44,6%) fulfilled criteria for diagnosis of MS. Three criteria were present in 30% of all patients, 4 criteria in 12,6%, and all criteria in 2%. Compared with hypertensives without MS, those who fulfilled criteria were significantly (p⬍0,0001) older (64,1 vs. 62,9), more frequently women (58 vs 53%) and sedentary (79,3 vs 73,9%). Moreover, they had increased BMI (32 vs 29,5 Kg/m2), higher systolic (2,2 mmHg), diastolic (0,8 mmHg), and pulse (1,4 mmHg) BP values, a poorer BP control (14,4 vs 27,8%) instead of a more frequent use of combined therapy (49,7 vs 40,5%). Other significant abnormalities present in patients with metabolic syndrome were higher serum total cholesterol (6,5 mg/dL), uric acid (0,4 mg/dL), and a decreased creatinine clearance as measured by the modified MDRD formula (76,4 vs 78,8 mL/min). Associate clinical conditions, such as coronary heart disease (7,8 vs 5,5%), heart failure (5,1 vs 3,2%), or peripheral artery disease (5 vs 3,1%) were also significantly more frequent (p⬍0,0001) in hypertensives with MS. In a logistic regression model, adjusting for those variables that are included in the definition of MS, female gender (OR: 3,9) and increased uric acid (OR: 1,076 for each mg/dL increase), were independently associated with metabolic syndrome. In conclusion, metabolic syndrome is present in almost half of an unselected hypertensive population. It is more frequent in women than in

men and it is associated with other abnormalities, specially increased uric acid. Metabolic syndrome patients are more refractory to BP treatment, even with an increased use of combined therapy and present a higher prevalence of associated clinical conditions. Key Words: Blood Pressure Control, Metabolic Syndrome, Obesity

P-520 OBESITY, WEIGHT LOSS AND HYPERTENSION Maria Leonarda De Rosa, Carmela Chiarolanza, Mariangela Esposito, Massimo Chiariello. Cardiology and Internal Medicine, University of Naples,Faculty of Medicine Federico II, Naples, Naples, Italy. The current scientific data indicate obesity as a risk factor for developing hypertension. The present study evaluated the impact of weight loss on clinical and instrumental parameters in a selected group of obese patients with H. An overall population of 345 H patients was sub-grouped on the basis of the Body Mass Index (BMI) :8.2% were under weight (BMI ⬍20.7 ), 63.9% normal weight ( BMI: 20.7-27.7 ), 19.6% overweight (BM I: 27.8-31 ), and 8.3% obese ( BMI ⬎31 ). Of the 96 overweight and obese patients 53 (55.2 % women, age 51-80 years ) accepted a tailored low-caloric dietary program for at least 4 months.The 53 patients belonged to both obese and overweight groups ( BMI ⬎ 27.8 ) and were in WHO classes I-II. Mean follow-up was 5 months. The mean loss of body weight was 4 Kg in 81.4% of patients,versus 3 Kg mean increase in whole (345 H patients) population (72.5-75.5 Kg). In the 53 patients we recorded a significant (p⬍0.05 ) improvement of WHO class,better control of arterial blood pressure and statistically significant (p ⬍0.05 ) lowering of total colesterol and triglyceride levels. Tailored dietetic program may improve clinical and instrumental parameters in patients with Hypertension. Key Words: Hypertension, Obesity, Weight Loss

P-521 EFFECT OF VALSARTAN ON ADIPONECTINE, LEPTIN AND RESISTINE IN HYPERTENSIVE OBESE PATIENTS Roberto Fogari, Giuseppe Derosa, Amedeo Mugellini, Paola Preti, Pierangelo Lazzari, Annalisa Zoppi, Andrea Rinaldi, Maurizio Destro. Department of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy. The aim of the study was to compare the effect of valsartan and amlodipine on blood pressure (BP), plasma adiponectine (pA), plasma leptin (pL), and plasma resistine (pR) in hypertensive patients with obesity. Seventy-two obese patients (BMI ⬎ 30 Kg/m2) with mild to moderate hypertension (DBP evaluated with appropriate size cuff ⬎ 90 mmHg ⬍ 110 mmHg) aged 31-65 years after a 4 week wash out period were randomized to valsartan 160 mg (n⫽ 36) or to amlodipine 10 mg (n⫽ 36) for 12 weeks. At the end of the wash-out period and of each treatment period BP was evaluated and a venous sample was drawn in the morning at the same hour to evaluate pA, pL and pR. Furthermore insulin resistance index (HOMA-R) was calculated using fasting glycemia and plasma insulin. No dietary advice was prescribed for the duration of the study. The main results are shown in the table.Both valsartan and amlodipine significantly decreased BP without any difference between the two treatments; however valsartan improved insulin sensitivity and induced a significant reduction in pL and pR and an increase in pA; such an increase was significantly correlated with HOMA-R changes. These data