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Role of moxonidine in insulin secretion and endothelial dysfunction in the patients with insulin resistance
202A
POSTERS: Metabolic Syndrome
Conclusions: Increased hs-CRP and fibrinogen levels are predictive of cardiac and cerebrovascular events and are significantly associated with arterial hypertension. Patients with MS have increased levels of CRP and fibrinogen and they have more frequently atherosclerotic carotid lesions, coronary artery disease and cerebrovascular disease if compared with patients with 0-2 RF. According to these data it may be advisable to treat patients with metabolic syndrome with secondary prevention strategy. Key Words: C Reactive Protein, Carotid Lesions, Methabolic Syndrome
P-536 INHIBITION OF THE RENIN-ANGIOTENSIN SYSTEM REDUCES VASCULAR OXIDATIVE STRESS AND VASCULAR DYSFUNCTION IN INSULIN-RESISTANT RATS Michael D Nyby, Karolin Abedi, Victoria Smutko, Pirooz Eslami, Morris Berger, Michael L Tuck. Department of Medicine and David Geffen School of Medicine, UCLA, Los Angeles, CA; Department of Medicine, VA Greater Los Angeles Healthcare System, Sepulveda, CA. The purpose of this study was to determine if oxidative stress and vascular dysfunction in insulin-resistant rats result from stimulation of the vascular renin-angiotensin system (RAS). Sprague-Dawley rats (8-10 weeks old) were separated into four groups of six rats each. The first group (CONT) was fed normal rat chow, the second group (CONT⫹CAP) was fed normal rat chow plus 500mg/l captopril in their drinking water, the third group (FFR) was fed a high fructose (60%) diet, and the fourth group (FFR⫹CAP) was fed the high fructose diet plus captopril-water. Systolic blood pressure (SBP) was measured by tail cuff, mesenteric artery vascular reactivity was measured using a video-imaging system, plasma hydrogen peroxide (H2O2) using an amplex red assay, plasma 8-Isoprostane by ELISA, and aortic tissue mRNA expression was determined by real-time RT-PCR. After 8 weeks, the SBP in the FFR group (143.7⫾1.2 mmHg) was significantly (P⬍0.05) higher than in the CONT (117.8⫾1.9) or FFR⫹CAP (120.2⫾2.3) groups. Mesenteric artery dose-response curves to acetylcholine were shifted to the right in FFR (P⬍0.05), but were similar to CONT in the FFR⫹CAP group. H2O2 was higher in FFR (23.3⫾4.3 mole/ml, P⬍0.02) compared to CONT (7.8⫾0.7) and was reduced towards CONT in the FFR⫹CAP (12.9⫾1.2). 8-isoprostane was significantly elevated in the FFR (112.6⫾7.3 pg/ml, P⬍0.05)compared to CONT (78.5⫾11.7) , and reduced in the FFR⫹CAP (82.5⫾8.3). RT-PCR of aortic tissue samples revealed that mRNA expression for angiotensin converting enzyme, angiotensin type 1 receptor (AT1R), and NOX4, a subunit of NADPH oxidase, were all increased in FFR relative to CONT (1.35⫾0.15, P⫽0.05; 2.48⫾0.49, P⬍0.02; and 3.08⫾0.32, P⬍0.01, -fold increase over CONT, respectively) In the FFR⫹CAP group, AT1R and NOX4 expression were reduced to CONT levels (0.52⫾0.11 and 0.833⫾0.46fold difference, respectively, P⬍0.01 vs. FFR for both). These results demonstrate that the vascular RAS is stimulated in insulin-resistant rats and this up-regulation is associated with vascular oxidative stress and dysfunction. Thus, the use of RAS inhibitors prevents these defects and improves vascular function in insulin-resistant conditions. Key Words: Insulin Resistance, Oxidative Stress, Renin-Angiotensin System
P-537 INFLUENCE OF COMPLEX TREATMENT WITH CANDESARTAN ON THE ENDOTHELIAL VASOREGULATION IN PATIENTS WITH INSULIN RESISTANCE Mariya A Orynchak, Evgen M Neyko, Olga S Chovganyuk, Vasyl E Neyko. Therapy, Ivano-Frankivsk State Medical Academy, Ivano-Frankivsk, Ukraine. Aim: To establish the role of the complex vascular-endothelial growth factor/endothelin-1 (VEGF/E-1) combined with different types of hyper-
AJH–May 2005–VOL. 18, NO. 5, PART 2
insulinemia (HI) for patients with arterial hypertension (AH) and insulin resistance (IR) under the prolonged treatment with enalapril and hydrochlorothiazide and possible correction by addition of candesartan. Materials and Methods: A group of 78 patients with AH stage II-III was examined. 43 patients had obesity and HI and 35 patients had normal level of immune-reactive insulin (IRI) in their blood (group of comparison). All patients received enalapril in doses of 20-40 mg/day and hydrochlorothiazide – 25-50 mg/day for 2-3 years. 43 patients with IR received candesartan at a dose of 4-8 mg/day for 3 weeks. Glucosetolerant tests (GTT) with simultaneous measurement of IRI and measurements of VEGF, E-1 were performed with immune-essay analysis with ELISA test kits. Results: In a group of comparison the IRI levels remained in the normal range under GTT: 6.38⫾0.72 mcU/ml before and 12.61⫾2.99 mcU/ml after 2 hours of GTT. The IRI levels in 27 patients (group II) was in the normal range before GTT but after GTT increased to 32.16⫾7.73 mcU/ml which corresponds to reactive HI. The IRI levels in 16 patients (group II) increased both before and after GTT to 28.79⫾6.84 mcU/ml and 38.18⫾9.41 mcU/ml (P⬍0.05) respectively (spontaneous HI). The concentrations of VEFG in blood equaled 29.80⫾4.73 ng/ml in the group of comparisons, 40.37⫾12.89 ng/ml in group I, 35.75⫾4.64 ng/ml in group II vs 19.33⫾2.09 ng/ml in the control (P⬍0.05). E-1 levels in blood increased along with the increase of HI stage. This equaled 2.63⫾0.95 pg/ml in the group of comparison, 3.83⫾1.08 pg/ml in group I (P⬍0.05), 11.36⫾1.06 pg/ml in group II vs 2.20⫾0.15 pg/ml in the control. The addition of candesartan to the complex treatment of AH helped to control BP in 80% of cases. Levels of HI, VEGF and E-1 decreased simultaneously to the values of the control and group I while in group II they showed a tendency to normalization. In conclusion, HI and endothelial dysfunction are preserved under prolonged treatment with enalapril and hydrochlorothiazide in patients with AH and IR. Candesartan increased the antihypertensive effect of enalapril and hydrochlorothiazide, decreased the HI level and normalized the endothelial vasoregulation especially under reactive HI. Key Words: Candesartan Treatment, Endothelial Vasoregulation, Insulin Resistance
P-538 ROLE OF MOXONIDINE IN INSULIN SECRETION AND ENDOTHELIAL DYSFUNCTION IN THE PATIENTS WITH INSULIN RESISTANCE Mariya A Orynchak, Evgen M Neyko, Olga S Chovganyuk. Therapy, Ivano-Frankivsk State Medical Academy, Ivano-Frankivsk, Ukraine. Aim: To establish possible correction of insulin resistance (IR) and endothelial dysfunction by I1-imidazolin receptor agonist – moxonidine in patients with arterial hypertension (AH) and IR. Methods: A group of 24 patients with AH stage II-III and obesity was examined. Patients were divided into 3 groups by blood levels of immune-reactive insulin (IRI). Group I included 6 with normal level of IRI ⬍ 5.7 mcU/ml. Group II had 10 with IRI in the range of 5.7 – 12.7 mcU/ml (mild hyperinsulinemia). Group III had 8 with IRI ⬎12.7 mcU/ml (obvious hyperinsulinemia). Glucose-tolerant tests (GTT) with simultaneous measurement of IRI, C-peptid, vascular-endothelial growth factor (VEGF) and endothelial-1 (E-1) blood levels were performed by immune-essay methods by ELISA test kits. The investigations were performed before and after 3 week treatments with moxonidine (phisiotens, Solvay Pharma, Germany) in doses of 4-8 mg/day along with basic therapy with enalapril and hydrochlorothiazide. Results: IRI levels in group I remained unchanged, in the normal range of 12.61⫾2.99 mcU/ml vs 6.38⫾0.72 mcU/ml in the control (P⬎0.05). C-peptid blood levels were equal to 2.81⫾0.91 ng/ml vs 1.67⫾0.68 ng/ml in the control (P⬎0.05). IRI blood levels in group II
AJH–May 2005–VOL. 18, NO. 5, PART 2
showed a tendency to decrease (P⬎0.05). C-peptid levels decreased by 34.62% (P⬍0.05) vs the control. IRI and C-peptid initial levels in group III increased by about 4 times compared to group I and the control (P⬍0.05). These factors decreased 25.81% (P⬍0.05) and 52.68% (P⬍0.05) compared to the initial values and the control. The concentration of VEGF in group I was twice as high as in the control at 29.80⫾4.73 ng/ml vs 19.33⫾2.09 ng/ml in the control (P⬍0.05). E-1 levels for group I did not change at 2.63⫾0.95 pg/ml vs 1.50⫾0.15 pg/ml in the control (P⬎0.05). VEGF level decreased to that of the control (P⬍0.05) and E-1 level remained at that value. VEGF levels in groups II and III appeared to be 1.5-2 times higher than the control. VEGF after treatment decreased but was still higher than the control by 22.65% (P⬍0.05). The E-1 blood levels in groups II and III were higher by a factor of 5 and 7 times (P⬍0.05) vs the control. E-1 levels decreased by a factor of 2-3, but did not reach the control. In conclusion, moxonidine decreased the level of hyperinsulinemia, normalized the insulin secretion and endothelial vasoregulation in patients with AH and IR. Key Words: Endothelial Dysfunction, Insulin Secretion, Moxonidine
P-539 PRESERVATION OF THE ARTERIAL PRESSURE RESPONSE TO LEPTIN IN DIET-INDUCED OBESE MICE: A POTENTIAL MECHANISM FOR OBESITY HYPERTENSION Kamal Rahmouni, Gina M Morgan, Donald A Morgan, Allyn L Mark, William G Haynes. Hypertension Genetics SCOR, CV Center and Department of Internal Medicine, University of Iowa, Iowa City, IA. We have previously demonstrated that diet-induced obese mice have selective resistance to leptin with preservation of the renal sympathetic nerve activity response to leptin despite loss of the feeding- and weightreducing actions of leptin. The preserved renal sympathetic response to leptin associated with the hyperleptinemia observed in mice on high fat diet might be expected to increase arterial pressure in these obese mice. To test the ability of leptin to increase arterial pressure in the obese mice we compared the action of intraperitoneal administration of leptin in mice on normal chow and high fat diet for 10 weeks. Radiotelemetric mean arterial pressure (MAP) was recorded in the conscious unrestrained state for 7 days. Lean and obese mice then received 12 days treatment with vehicle or leptin (60 mg, twice daily, IP) with continued MAP recordings. After 10 weeks, mice on high fat diet weighed about 10% more than those fed the normal chow (30.8⫾0.2 vs.27.9⫾0.2 g, P⬍0.001). Mice on high fat diet showed higher baseline MAP than the mice on normal chow (110⫾1 vs. 100⫾1 mmHg, P⬍0.001). In mice on normal chow, 12-day leptin treatment caused a significant increase in MAP as expected (⫹9⫾6 and -2⫾2.mmHg for leptin- and vehicle-treated mice respectively, P⬍0.001). Leptin caused also a significant increase in MAP in the high fat-fed mice (⫹6⫾5 vs. -5⫾1 mmHg, P⬍0.01). Leptin treatment caused a significant decrease in body weight, food intake and fat mass in mice on normal chow, but not in the high fat-fed mice. This study demonstrates that there is preservation of the arterial pressure response to leptin in a dietary model of obesity despite resistance to the appetite and weight reducing actions of leptin. This represents a potential mechanism for increases in arterial pressure and adverse cardiovascular actions of leptin in obesity. Key Words: Hypertension, Leptin, Obesity
POSTERS: Metabolic Syndrome
203A
P-540 METABOLIC SYNDROME INCREASES THE RISK OF HYPERTENSION-INDUCED ORGAN DAMAGE IN HYPERTENSIVES ATTENDING PRIMARY CARE CENTERS. ERIC-HTN STUDY Josep Redon, Jose V Lozano, Luis Cea-Calvo, Cristina Fernandez-Perez, Jorge Navarro, Alvaro Bonet, Jorge Gonzalez-Esteban. Hypertension Clinic, Hospital Clinico, University of Valencia, Valencia, Spain; Health Care Center, Serreria, 2, Valencia, Spain; Department of Clinical Research, Merck, Sharp & Dhome, Madrid, Spain; Research Unit, Hospital Clinico San Carlos, University Complutense, Madrid, Spain; Health Care Center, Salvador Pau, Valencia, Spain. The objective was to assess the influence of metabolic syndrome on hypertension-related organ damage (left ventricular hypertrophy and renal function) in a large survey of hypertensives who attend primary care clinics. Subjects and Methods: Hypertensive subjects of both genders, aged ⬎55 years were randomly selected among those attending primary care centers all over Spain. In all subjects, the existence of cardiovascular disease and cardiovascular risk factor status (body mass index, baseline glucose, lipid profile, and diabetes) were assessed. The EKG-left ventricular hypertrophy was assessed by using the Cornell criteria, and glomerular filtration rates were calculated using the Cockroft-Gault formula. Metabolic Syndrome was defined according the NECP, in which BMI ⬎28,8 kg/m2 for males and ⬎26,2 kg/m2 for females instead of waist circumference was considered as a criteria. Risk for LV hypertrophy and/or renal insufficiency were sougth by using a logistic regression analysis in which age, sex, and body mass index were included. Results: A total of 12857 subjects (mean age 67,6 years, 55,4% women) were included. After adjusting for age, sex and BMI, the relative risk for LV hypertrophy was significantly higher in diabetics 2,0 [1,8-2,2] and in non-diabetics with Metabolic Syndrome 1,4 [1,2-1,6] as compared with non-diabetic in absence of Metabolic Syndrome (p⬍0.001). Likewise, risk for renal failure was also significantly higher for diabetics 1,6 [1,5-1,8] and for non-diabetics with Metabolic Syndrome 1,3 [1,2-1,5], (p⬍0.001). Conclusions: In a population of hypertensives going to primary care facilities, metabolic syndrome was accompanied by a higher prevalence of hypertension-induced organ damage, LV hypertrophy and renal insufficiency. Diabetes further increases the risk. Key Words: Left Ventricular Hypertrophy, Metabolic Syndrome, Renal Function
P-541 A ACTIVATED IMMUNE SYSTEM AS A CAUSE OR AN EFFECT OF THE SYNDROME X. THE IMPORTANCE OF THE C3 Olivia Sanchez, Rosa Fabregate, Moises Rubio, Enrique Bernal, Martin Fabregate, Eva Fernandez, Begonia Monge, Judith Marquez, Jose Saban-Ruiz. Endothelial Pathology Unit, Ramon y Cajal Hospital, Madrid, Madrid, Spain. Introduction: Pickup has pointed out the role played by the immune system in the pathogenesis of the metabolic syndrome, specially in type 2 diabetic (DM2) patients. However, its participation in the early stages of this disease remains unknown. On the other hand, all its clinical and biochemical components are known to lead to atherosclerotic disease via complex mechanisms. The activation of the complement system stands out in this process, particularly through the C3 component. Nevertheless, its importance as a marker of insulin resistance (IR) deserves further investigation. Aims: 1. To characterize a cardiovascular risk population according to its C3 serum levels. 2. To correlate such levels with anthropometric and metabolic parameters.
POSTERS: Metabolic Syndrome
Conclusions: Increased hs-CRP and fibrinogen levels are predictive of cardiac and cerebrovascular events and are significantly associated with arterial hypertension. Patients with MS have increased levels of CRP and fibrinogen and they have more frequently atherosclerotic carotid lesions, coronary artery disease and cerebrovascular disease if compared with patients with 0-2 RF. According to these data it may be advisable to treat patients with metabolic syndrome with secondary prevention strategy. Key Words: C Reactive Protein, Carotid Lesions, Methabolic Syndrome
P-536 INHIBITION OF THE RENIN-ANGIOTENSIN SYSTEM REDUCES VASCULAR OXIDATIVE STRESS AND VASCULAR DYSFUNCTION IN INSULIN-RESISTANT RATS Michael D Nyby, Karolin Abedi, Victoria Smutko, Pirooz Eslami, Morris Berger, Michael L Tuck. Department of Medicine and David Geffen School of Medicine, UCLA, Los Angeles, CA; Department of Medicine, VA Greater Los Angeles Healthcare System, Sepulveda, CA. The purpose of this study was to determine if oxidative stress and vascular dysfunction in insulin-resistant rats result from stimulation of the vascular renin-angiotensin system (RAS). Sprague-Dawley rats (8-10 weeks old) were separated into four groups of six rats each. The first group (CONT) was fed normal rat chow, the second group (CONT⫹CAP) was fed normal rat chow plus 500mg/l captopril in their drinking water, the third group (FFR) was fed a high fructose (60%) diet, and the fourth group (FFR⫹CAP) was fed the high fructose diet plus captopril-water. Systolic blood pressure (SBP) was measured by tail cuff, mesenteric artery vascular reactivity was measured using a video-imaging system, plasma hydrogen peroxide (H2O2) using an amplex red assay, plasma 8-Isoprostane by ELISA, and aortic tissue mRNA expression was determined by real-time RT-PCR. After 8 weeks, the SBP in the FFR group (143.7⫾1.2 mmHg) was significantly (P⬍0.05) higher than in the CONT (117.8⫾1.9) or FFR⫹CAP (120.2⫾2.3) groups. Mesenteric artery dose-response curves to acetylcholine were shifted to the right in FFR (P⬍0.05), but were similar to CONT in the FFR⫹CAP group. H2O2 was higher in FFR (23.3⫾4.3 mole/ml, P⬍0.02) compared to CONT (7.8⫾0.7) and was reduced towards CONT in the FFR⫹CAP (12.9⫾1.2). 8-isoprostane was significantly elevated in the FFR (112.6⫾7.3 pg/ml, P⬍0.05)compared to CONT (78.5⫾11.7) , and reduced in the FFR⫹CAP (82.5⫾8.3). RT-PCR of aortic tissue samples revealed that mRNA expression for angiotensin converting enzyme, angiotensin type 1 receptor (AT1R), and NOX4, a subunit of NADPH oxidase, were all increased in FFR relative to CONT (1.35⫾0.15, P⫽0.05; 2.48⫾0.49, P⬍0.02; and 3.08⫾0.32, P⬍0.01, -fold increase over CONT, respectively) In the FFR⫹CAP group, AT1R and NOX4 expression were reduced to CONT levels (0.52⫾0.11 and 0.833⫾0.46fold difference, respectively, P⬍0.01 vs. FFR for both). These results demonstrate that the vascular RAS is stimulated in insulin-resistant rats and this up-regulation is associated with vascular oxidative stress and dysfunction. Thus, the use of RAS inhibitors prevents these defects and improves vascular function in insulin-resistant conditions. Key Words: Insulin Resistance, Oxidative Stress, Renin-Angiotensin System
P-537 INFLUENCE OF COMPLEX TREATMENT WITH CANDESARTAN ON THE ENDOTHELIAL VASOREGULATION IN PATIENTS WITH INSULIN RESISTANCE Mariya A Orynchak, Evgen M Neyko, Olga S Chovganyuk, Vasyl E Neyko. Therapy, Ivano-Frankivsk State Medical Academy, Ivano-Frankivsk, Ukraine. Aim: To establish the role of the complex vascular-endothelial growth factor/endothelin-1 (VEGF/E-1) combined with different types of hyper-
AJH–May 2005–VOL. 18, NO. 5, PART 2
insulinemia (HI) for patients with arterial hypertension (AH) and insulin resistance (IR) under the prolonged treatment with enalapril and hydrochlorothiazide and possible correction by addition of candesartan. Materials and Methods: A group of 78 patients with AH stage II-III was examined. 43 patients had obesity and HI and 35 patients had normal level of immune-reactive insulin (IRI) in their blood (group of comparison). All patients received enalapril in doses of 20-40 mg/day and hydrochlorothiazide – 25-50 mg/day for 2-3 years. 43 patients with IR received candesartan at a dose of 4-8 mg/day for 3 weeks. Glucosetolerant tests (GTT) with simultaneous measurement of IRI and measurements of VEGF, E-1 were performed with immune-essay analysis with ELISA test kits. Results: In a group of comparison the IRI levels remained in the normal range under GTT: 6.38⫾0.72 mcU/ml before and 12.61⫾2.99 mcU/ml after 2 hours of GTT. The IRI levels in 27 patients (group II) was in the normal range before GTT but after GTT increased to 32.16⫾7.73 mcU/ml which corresponds to reactive HI. The IRI levels in 16 patients (group II) increased both before and after GTT to 28.79⫾6.84 mcU/ml and 38.18⫾9.41 mcU/ml (P⬍0.05) respectively (spontaneous HI). The concentrations of VEFG in blood equaled 29.80⫾4.73 ng/ml in the group of comparisons, 40.37⫾12.89 ng/ml in group I, 35.75⫾4.64 ng/ml in group II vs 19.33⫾2.09 ng/ml in the control (P⬍0.05). E-1 levels in blood increased along with the increase of HI stage. This equaled 2.63⫾0.95 pg/ml in the group of comparison, 3.83⫾1.08 pg/ml in group I (P⬍0.05), 11.36⫾1.06 pg/ml in group II vs 2.20⫾0.15 pg/ml in the control. The addition of candesartan to the complex treatment of AH helped to control BP in 80% of cases. Levels of HI, VEGF and E-1 decreased simultaneously to the values of the control and group I while in group II they showed a tendency to normalization. In conclusion, HI and endothelial dysfunction are preserved under prolonged treatment with enalapril and hydrochlorothiazide in patients with AH and IR. Candesartan increased the antihypertensive effect of enalapril and hydrochlorothiazide, decreased the HI level and normalized the endothelial vasoregulation especially under reactive HI. Key Words: Candesartan Treatment, Endothelial Vasoregulation, Insulin Resistance
P-538 ROLE OF MOXONIDINE IN INSULIN SECRETION AND ENDOTHELIAL DYSFUNCTION IN THE PATIENTS WITH INSULIN RESISTANCE Mariya A Orynchak, Evgen M Neyko, Olga S Chovganyuk. Therapy, Ivano-Frankivsk State Medical Academy, Ivano-Frankivsk, Ukraine. Aim: To establish possible correction of insulin resistance (IR) and endothelial dysfunction by I1-imidazolin receptor agonist – moxonidine in patients with arterial hypertension (AH) and IR. Methods: A group of 24 patients with AH stage II-III and obesity was examined. Patients were divided into 3 groups by blood levels of immune-reactive insulin (IRI). Group I included 6 with normal level of IRI ⬍ 5.7 mcU/ml. Group II had 10 with IRI in the range of 5.7 – 12.7 mcU/ml (mild hyperinsulinemia). Group III had 8 with IRI ⬎12.7 mcU/ml (obvious hyperinsulinemia). Glucose-tolerant tests (GTT) with simultaneous measurement of IRI, C-peptid, vascular-endothelial growth factor (VEGF) and endothelial-1 (E-1) blood levels were performed by immune-essay methods by ELISA test kits. The investigations were performed before and after 3 week treatments with moxonidine (phisiotens, Solvay Pharma, Germany) in doses of 4-8 mg/day along with basic therapy with enalapril and hydrochlorothiazide. Results: IRI levels in group I remained unchanged, in the normal range of 12.61⫾2.99 mcU/ml vs 6.38⫾0.72 mcU/ml in the control (P⬎0.05). C-peptid blood levels were equal to 2.81⫾0.91 ng/ml vs 1.67⫾0.68 ng/ml in the control (P⬎0.05). IRI blood levels in group II
AJH–May 2005–VOL. 18, NO. 5, PART 2
showed a tendency to decrease (P⬎0.05). C-peptid levels decreased by 34.62% (P⬍0.05) vs the control. IRI and C-peptid initial levels in group III increased by about 4 times compared to group I and the control (P⬍0.05). These factors decreased 25.81% (P⬍0.05) and 52.68% (P⬍0.05) compared to the initial values and the control. The concentration of VEGF in group I was twice as high as in the control at 29.80⫾4.73 ng/ml vs 19.33⫾2.09 ng/ml in the control (P⬍0.05). E-1 levels for group I did not change at 2.63⫾0.95 pg/ml vs 1.50⫾0.15 pg/ml in the control (P⬎0.05). VEGF level decreased to that of the control (P⬍0.05) and E-1 level remained at that value. VEGF levels in groups II and III appeared to be 1.5-2 times higher than the control. VEGF after treatment decreased but was still higher than the control by 22.65% (P⬍0.05). The E-1 blood levels in groups II and III were higher by a factor of 5 and 7 times (P⬍0.05) vs the control. E-1 levels decreased by a factor of 2-3, but did not reach the control. In conclusion, moxonidine decreased the level of hyperinsulinemia, normalized the insulin secretion and endothelial vasoregulation in patients with AH and IR. Key Words: Endothelial Dysfunction, Insulin Secretion, Moxonidine
P-539 PRESERVATION OF THE ARTERIAL PRESSURE RESPONSE TO LEPTIN IN DIET-INDUCED OBESE MICE: A POTENTIAL MECHANISM FOR OBESITY HYPERTENSION Kamal Rahmouni, Gina M Morgan, Donald A Morgan, Allyn L Mark, William G Haynes. Hypertension Genetics SCOR, CV Center and Department of Internal Medicine, University of Iowa, Iowa City, IA. We have previously demonstrated that diet-induced obese mice have selective resistance to leptin with preservation of the renal sympathetic nerve activity response to leptin despite loss of the feeding- and weightreducing actions of leptin. The preserved renal sympathetic response to leptin associated with the hyperleptinemia observed in mice on high fat diet might be expected to increase arterial pressure in these obese mice. To test the ability of leptin to increase arterial pressure in the obese mice we compared the action of intraperitoneal administration of leptin in mice on normal chow and high fat diet for 10 weeks. Radiotelemetric mean arterial pressure (MAP) was recorded in the conscious unrestrained state for 7 days. Lean and obese mice then received 12 days treatment with vehicle or leptin (60 mg, twice daily, IP) with continued MAP recordings. After 10 weeks, mice on high fat diet weighed about 10% more than those fed the normal chow (30.8⫾0.2 vs.27.9⫾0.2 g, P⬍0.001). Mice on high fat diet showed higher baseline MAP than the mice on normal chow (110⫾1 vs. 100⫾1 mmHg, P⬍0.001). In mice on normal chow, 12-day leptin treatment caused a significant increase in MAP as expected (⫹9⫾6 and -2⫾2.mmHg for leptin- and vehicle-treated mice respectively, P⬍0.001). Leptin caused also a significant increase in MAP in the high fat-fed mice (⫹6⫾5 vs. -5⫾1 mmHg, P⬍0.01). Leptin treatment caused a significant decrease in body weight, food intake and fat mass in mice on normal chow, but not in the high fat-fed mice. This study demonstrates that there is preservation of the arterial pressure response to leptin in a dietary model of obesity despite resistance to the appetite and weight reducing actions of leptin. This represents a potential mechanism for increases in arterial pressure and adverse cardiovascular actions of leptin in obesity. Key Words: Hypertension, Leptin, Obesity
POSTERS: Metabolic Syndrome
203A
P-540 METABOLIC SYNDROME INCREASES THE RISK OF HYPERTENSION-INDUCED ORGAN DAMAGE IN HYPERTENSIVES ATTENDING PRIMARY CARE CENTERS. ERIC-HTN STUDY Josep Redon, Jose V Lozano, Luis Cea-Calvo, Cristina Fernandez-Perez, Jorge Navarro, Alvaro Bonet, Jorge Gonzalez-Esteban. Hypertension Clinic, Hospital Clinico, University of Valencia, Valencia, Spain; Health Care Center, Serreria, 2, Valencia, Spain; Department of Clinical Research, Merck, Sharp & Dhome, Madrid, Spain; Research Unit, Hospital Clinico San Carlos, University Complutense, Madrid, Spain; Health Care Center, Salvador Pau, Valencia, Spain. The objective was to assess the influence of metabolic syndrome on hypertension-related organ damage (left ventricular hypertrophy and renal function) in a large survey of hypertensives who attend primary care clinics. Subjects and Methods: Hypertensive subjects of both genders, aged ⬎55 years were randomly selected among those attending primary care centers all over Spain. In all subjects, the existence of cardiovascular disease and cardiovascular risk factor status (body mass index, baseline glucose, lipid profile, and diabetes) were assessed. The EKG-left ventricular hypertrophy was assessed by using the Cornell criteria, and glomerular filtration rates were calculated using the Cockroft-Gault formula. Metabolic Syndrome was defined according the NECP, in which BMI ⬎28,8 kg/m2 for males and ⬎26,2 kg/m2 for females instead of waist circumference was considered as a criteria. Risk for LV hypertrophy and/or renal insufficiency were sougth by using a logistic regression analysis in which age, sex, and body mass index were included. Results: A total of 12857 subjects (mean age 67,6 years, 55,4% women) were included. After adjusting for age, sex and BMI, the relative risk for LV hypertrophy was significantly higher in diabetics 2,0 [1,8-2,2] and in non-diabetics with Metabolic Syndrome 1,4 [1,2-1,6] as compared with non-diabetic in absence of Metabolic Syndrome (p⬍0.001). Likewise, risk for renal failure was also significantly higher for diabetics 1,6 [1,5-1,8] and for non-diabetics with Metabolic Syndrome 1,3 [1,2-1,5], (p⬍0.001). Conclusions: In a population of hypertensives going to primary care facilities, metabolic syndrome was accompanied by a higher prevalence of hypertension-induced organ damage, LV hypertrophy and renal insufficiency. Diabetes further increases the risk. Key Words: Left Ventricular Hypertrophy, Metabolic Syndrome, Renal Function
P-541 A ACTIVATED IMMUNE SYSTEM AS A CAUSE OR AN EFFECT OF THE SYNDROME X. THE IMPORTANCE OF THE C3 Olivia Sanchez, Rosa Fabregate, Moises Rubio, Enrique Bernal, Martin Fabregate, Eva Fernandez, Begonia Monge, Judith Marquez, Jose Saban-Ruiz. Endothelial Pathology Unit, Ramon y Cajal Hospital, Madrid, Madrid, Spain. Introduction: Pickup has pointed out the role played by the immune system in the pathogenesis of the metabolic syndrome, specially in type 2 diabetic (DM2) patients. However, its participation in the early stages of this disease remains unknown. On the other hand, all its clinical and biochemical components are known to lead to atherosclerotic disease via complex mechanisms. The activation of the complement system stands out in this process, particularly through the C3 component. Nevertheless, its importance as a marker of insulin resistance (IR) deserves further investigation. Aims: 1. To characterize a cardiovascular risk population according to its C3 serum levels. 2. To correlate such levels with anthropometric and metabolic parameters.