Metabolic syndrome: comparison of the two commonly used animal models.

BACKGROUND: The etiology of the metabolic syndrome (MS) includes both genetic and environmental factors. The two most commonly studied animal models of the MS are the high-sucrose diet given to spontaneously hypertensive rats (SHRs) and high-fructose diet given to Sprague Dawley rats (SDRs). This study compares between these two models. METHODS: The two rat strains were examined; within each group, the rats were assigned to either the high-sugar diet (SDRs with fructose-enriched diet and SHRs with sucrose-enriched diet) or standard rat chow (control group). The rats were followed for 7 weeks. The main MS components (obesity, hypertension, impaired glucose tolerance, hyperinsulinemia, hypertriglyceridemia, and hypercholesterolemia) were measured. RESULTS: At baseline systolic blood pressure (SBP), fasting blood levels of triglycerides and insulin, as well as glucose intolerance, were significantly higher among the SHRs compared to SDRs. Following fructose enrichment, SDRs became hyperinsulinemic, hypertriglyceridemic, hypercholesterolemic, hypertensive, and insulin resistant, whereas SHRs responded to sucrose supplementation by a significant elevation in blood pressure and mild worsening of insulin resistance. Endpoint results revealed superiority of sucrose--SHR model in terms of hypertension and superiority of fructose--SDR model in terms of hyperinsulinemia, hypertriglyceridemia, and hypercholesterolemia. Both models showed similar postintervention degree of glucose tolerance. CONCLUSIONS: The fructose-fed SDR model represents a predominantly environmentally acquired MS, whereas the SHR model is less affected by dietary intervention and better displays the predominantly genetic spontaneous appearance of the syndrome. This fundamental difference should be taken into consideration when choosing an animal model to study the MS.

Effect of PPAR-gamma agonist on adiponectin levels in the metabolic syndrome: lessons from the high fructose fed rat model.

BACKGROUND: The health hazard of the metabolic syndrome (MS) is increasing, yet there is no effective pharmacologic treatment to this entity as a whole. Recently, hypoadiponectinemia was found to play an important role in the development of MS. We studied the effect of the PPAR-gamma agonist rosiglitazone on adiponectin and the metabolic profile in the fructose-induced hypertensive, hyperinsulinemic, hypertriglyceridemic rat model. METHODS: Thirty male Sprague-Dawley rats were divided into three groups. Ten were fed standard rat chow for 5 weeks, 10, a fructose-enriched diet for 5 weeks, and 10, a fructose-enriched diet for 5 weeks, with rosiglitazone 10 mg/kg/d added during the last 2 weeks. Blood pressure (BP), oral glucose tolerance test (OGTT), plasma insulin, triglycerides, and adiponectin were recorded, as well as mRNA levels of the adiponectin gene in visceral adipose tissue. RESULTS: Fructose-fed rats developed MS as manifested by the increase in systolic BP (from 139 +/- 3 to 158 +/- 4 mm Hg, P < .05), insulin (from 26 +/- 1.6 to 40 +/- 2.5 muU/mL, P < .05), triglycerides (from 91 +/- 9 to 304 +/- 24 mg/dL, P < .05), and impaired OGTT (area under the curve from 13,894 +/- 246 to 17,725 +/- 700 mg/dL/min). Treatment with rosiglitazone reversed these effects and reduced BP to 133 +/- 7 mm Hg, insulin levels to 30 +/- 2.8 muU/mL, triglycerides to 116 +/- 9 mg/dL, and the OGTT to 15,415 +/- 372 mg/dL/min (P < .05 for all variables). In addition, rosiglitazone increased plasma levels of adiponectin fourfold from 4.3 +/- 0.1 to 18.4 +/- 0.6 mug/mL (P < .05). This increase was coupled with 3.8-fold increase in adiponectin mRNA in visceral adipose tissue. CONCLUSIONS: This study shows for the first time that in an animal model of MS, the insulin sensitizer, rosiglitazone, improves the metabolic profile and increases plasma levels of adiponectin and its gene expression. It is possible therefore that rosiglitazone exerts its beneficial effects by increasing the levels of adiponectin.

Antianxiety treatment in patients with excessive hypertension.

OBJECTIVE: There are no guidelines on how to treat patients with excessive hypertension. Anxiety is a common cause of excessive hypertension and therefore antianxiety treatment may be beneficial in these patients. We therefore compared the efficacy and safety of antianxiety treatment with sublingual captopril administration in patients with excessive hypertension and no evidence of acute target organ damage. METHODS: Thirty-six patients (28 women and 8 men), mean age 60 +/- 2 years (range 36 to 85 years) who were referred to the emergency room because of excessive hypertension (>190/100 mm Hg) without evidence of acute target organ damage were randomized to receive either oral diazepam, 5 mg (n = 17, study group) or sublingual captopril, 25 mg (n = 19, control group). Blood pressure (BP) and heart rate were recorded hourly for 3 h. RESULTS: Both treatments decreased BP significantly (from 213 +/- 5/105 +/- 3 to 170 +/- 8/88 +/- 6 mm Hg in the study group, and from 208 +/- 5/107 +/- 3 to 181 +/- 8/95 +/- 3 mm Hg in the control group (P < .01 v initial BP). One patient in each group was hospitalized because of sustained excessive hypertension. CONCLUSIONS: Antianxiety treatment is effective in lowering BP in patients with excessive hypertension. Thus, anxiolytic treatment may be considered in patients with excessive hypertension without acute target organ damage. Further large placebo controlled studies are required to prove the benefit of anxiolytic agents.

Does dietary recall adequately assess sodium, potassium, and calcium intake in hypertensive patients?

OBJECTIVE: A diet low in sodium, high in potassium, and high in calcium is recommended to lower blood pressure. However, compliance with this diet is poor, probably because of dietary intake underestimation. Therefore, we compared electrolyte intake as estimated from dietary recall with a 24-h urinary excretion. METHODS: Thirty-six patients (26 men and 10 women) with a mean age of 46 +/- 8 y participated in the study. All participants had essential hypertension and were on no drug therapy (n = 20) or non-diuretic monotherapy (n = 16). Patients were instructed to consume a low-sodium (50 mmol/d), high-potassium (supplementation with 30 to 60 mmol/d), and high-calcium (1000 mg/d) diet. Compliance with the diet was assessed at baseline and then 1, 2, and 3 mo after starting the diet. Sodium, potassium, and calcium intakes were carefully estimated from patients' dietary recall and 24-h urinary collection. RESULTS: Estimated sodium intake significantly correlated with 24-h urinary excretion (R = 0.43 P < 0.001). However, estimated sodium intake was lower than urinary sodium excretion by 34% at baseline and by 47% after 3 mo of dieting (P < 0.05). Estimated potassium intake correlated with 24-h urinary excretion. Estimated calcium intake significantly increased from 933 +/- 83 mg/d to 1029 +/- 171 mg/d (P < 0.05). Calcium intake derived from patients' recall far exceeded and only slightly correlated with 24-h urinary excretion (R = 0.23, P < 0.01). CONCLUSIONS: Patients tend to underestimate their sodium intake by 30% to 50%; therefore, urinary sodium excretion is more accurate to assess sodium intake. Thus, 24-h urinary sodium excretion should be used in clinical practice and in clinical trials, especially when dietary non-compliance is suspected.

Clinical outcomes and cost effectiveness of accelerated diagnostic protocol in a chest pain center compared with routine care of patients with chest pain.

AIMS: The aim of this study was to compare in patients presenting with acute chest pain the clinical outcomes and cost-effectiveness of an accelerated diagnostic protocol utilizing contemporary technology in a chest pain unit versus routine care in an internal medicine department. METHODS AND RESULTS: Hospital and 90-day course were prospectively studied in 585 consecutive low-moderate risk acute chest pain patients, of whom 304 were investigated in a designated chest pain center using a pre-specified accelerated diagnostic protocol, while 281 underwent routine care in an internal medicine ward. Hospitalization was longer in the routine care compared with the accelerated diagnostic protocol group (p<0.001). During hospitalization, 298 accelerated diagnostic protocol patients (98%) vs. 57 (20%) routine care patients underwent non-invasive testing, (p<0.001). Throughout the 90-day follow-up, diagnostic imaging testing was performed in 125 (44%) and 26 (9%) patients in the routine care and accelerated diagnostic protocol patients, respectively (p<0.001). Ultimately, most patients in both groups had non-invasive imaging testing. Accelerated diagnostic protocol patients compared with those receiving routine care was associated with a lower incidence of readmissions for chest pain [8 (3%) vs. 24 (9%), p<0.01], and acute coronary syndromes [1 (0.3%) vs. 9 (3.2%), p<0.01], during the follow-up period. The accelerated diagnostic protocol remained a predictor of lower acute coronary syndromes and readmissions after propensity score analysis [OR = 0.28 (CI 95% 0.14-0.59)]. Cost per patient was similar in both groups [($2510 vs. $2703 for the accelerated diagnostic protocol and routine care group, respectively, (p = 0.9)]. CONCLUSION: An accelerated diagnostic protocol is clinically superior and as cost effective as routine in acute chest pain patients, and may save time and resources.