Background. The etiology of the metabolic syndrome (MS) includes both genetic and environmental factors. The two most commonly studied animal models of

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. 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. 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. 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.

Background High sodium intake is associated with increased risk of end-organ damage, independent of blood pressure (BP) levels. The protective peptide adiponectin may play a role in the pathogenesis of hypertension and particularly in salt-loaded conditions. Furthermore, increased adiponectin levels were observed in salt-loaded conditions. However, there is little information on the direct effect of high-salt diet on plasma adiponectin. The aim of the present study was to examine the effect of high-salt diet on adiponectin levels in Sprague–Dawley rats and explore the mechanisms that regulate adiponectin levels under salt loading. Methods Sprague–Dawley rats were fed either standard chow diet or medium or high sodium diet for 5 weeks. BP and plasma adiponectin were measured at baseline and during the study. In additional studies the same protocol was repeated with the addition of clonidine, telmisartan, hydralazine or eplerenone. Results High-salt diet increased systolic BP, suppressed plasma aldosterone levels and attenuated body weight gain. Five weeks of salt loading increased plasma adiponectin levels in a dose-dependant manner (medium salt and high salt were 47 and 93% higher than control, respectively, P < 0.05). Hydralazine and clonidine attenuated salt-induced BP increase but did not attenuate the increase in adiponectin levels whereas, telmisartan, an angiotensin receptor blocker, and eplerenone, an aldosterone blocker, attenuated both the increase in BP and in adiponectin levels. Conclusions High salt intake increases adiponectin levels independent of the increase in BP. This effect is mediated through the renin–angiotensin–aldosterone system.

Recent reports indicate that Parkinson's disease (PD) involves specific functional abnormalities in residual neurons – decreased vesicular sequestration of cytoplasmic catecholamines via the vesicular monoamine transporter (VMAT) and decreased aldehyde dehydrogenase (ALDH) activity. This double hit builds up the autotoxic metabolite 3,4-dihydroxyphenylacetaldehyde (DOPAL), the focus of the catecholaldehyde hypothesis for the pathogenesis of PD. An animal model is needed that reproduces this abnormal catecholamine neurochemical pattern. Adult rats received subcutaneous vehicle or the mitochondrial complex 1 inhibitor rotenone (2 mg/kg/day via a minipump) for 10 days. Locomotor activity was recorded, and striatal tissue sampled for catechol contents and catechol ratios that indicate the above abnormalities. Compared to vehicle, rotenone reduced locomotor activity (P=0.002), decreased tissue dopamine concentrations (P=0.00001), reduced indices of vesicular sequestration (3,4-dihydroxyphenylacetic acid (DOPAC)/dopamine) and ALDH activity (DOPAC/DOPAL) (P=0.0025, P=0.036), and increased DOPAL levels (P=0.04). The rat rotenone model involves functional abnormalities in catecholaminergic neurons that replicate the pattern found in PD putamen. These include a vesicular storage defect, decreased ALDH activity and DOPAL build-up. The rat rotenone model provides a suitable in vivo platform for studying the catecholaldehyde hypothesis.

Hypertension is one of the most important risk factors for cardiovascular morbidity and mortality. Recently it has been suggested that the amino acid homocysteine contributes to this process. This study evaluates whether elevated plasma levels of homocysteine in hypertensive patients are associated with increased risk for cardiovascular events. Fifty hypertensive patients with a documented history of cerebral or cardiac events were age and gender matched to 50 hypertensive patients with no evidence of any cerebral or cardiac event. Demographic details, duration of hypertension, presence of other risk factors, and use of antihypertensive medications were recorded for each patient. Plasma levels of homocysteine were measured by high-performance liquid chromatography technology. The two groups had similar demographic parameters, with a mean age of 64.6 +/- 9.4 years. Patients with cardiovascular events were more likely to be past smokers and to have been treated with calcium antagonists, aspirin, and nitrates. Homocysteine levels were 12.1 +/- 5.8 micromol/L in those with documented cardiovascular disease and 11.1 +/- 4.7 micromol/L in those without (P = NS). Levels of plasma homocysteine were higher in those with hypercholesterolemia (P = .03) and in smokers, and tended to be lower in those who used beta-blockers, angiotensin converting enzyme (ACE) inhibitors, diuretics, and nitrates. Thus, hyperhomocysteinemia is not a feature of hypertensive patients with atherothrombotic events and there is no support for additive or synergistic effects between these two independent risk factors.