Francisco Rosa

Tejido adiposo epicárdico y su asociación con niveles plasmáticos de adrenomedulina en pacientes con síndrome metabólico

OBJECTIVE To assess the association between epicardial adipose tissue thickness (EAT) and plasma adrenomedullin plasma levels in patients with metabolic syndrome (MS). METHODS Twenty-one patients (12 females and 9 males) with MS according to the International Diabetes Federation guidelines, aged 22-58 years, were enrolled into the study and compared to 19 age-matched control subjects without MS. Plasma glucose, lipid, and adrenomedullin levels were assessed. EAT, left ventricular mass, and carotid intima-media thickness were evaluated by transthoracic two-dimensional echocardiography. RESULTS No statistically significant differences were found between the groups in age, sex, and height. Body weight, abdominal circumference (AC), body mass index (BMI), systolic blood pressure (SBP), and diastolic blood pressure (DBP) were significantly higher (p=0.0001) in MS patients; this group also showed significantly higher glucose (p=0.001), total cholesterol (p=0.01), LDL-C (p=0.03), VLDL-C (p=0.005), triglyceride (p=0.002), Tg/HDL ratio (p=0.0001), and plasma adrenomedullin (3.49±1.21 vs 1.69±0.92 ng/mL; p=0.0001) levels and lower HDL-C (p=0.02) levels as compared to the control group. EAT was significantly thicker in MS patients compared to the control group (8.45±3.14 vs 5.43±0.96; p=0.0001), showed a positive correlation to BMI (r=0.347; p=0.02), AC (r=0.350; p=0.02), DBP (r=0.346; p=0.02), and adrenomedullin levels (r=0.741; p=0.0001). In multiple linear regression analysis, adrenomedullin was the only parameter associated to EAT (R(2)=0.550; p=0.0001). CONCLUSION In this small patient group, a statistically significant association was found between EAT and plasma adrenomedullin levels, which may be considered as a potential biomarker of MS.

Testosterone and Nandrolone Sensitization of Brain Anteroventral Area of Third Ventricle to Hypertonic NaCl-Induced Sympathetic Response

Androgenic steroids increase atherogenesis, thrombogenicity and endothelial dysfunction when administered in high doses, however their effects on NaCl sensitivity of the brain anteroventral area of the third ventricle (ΔV3V) have not been explored. Sprague-Dawley male rats were anesthetized with sodium pentobarbital (40 mg/kg) and the femoral intra-arterial blood pressure and heart rate monitored through a strain-gauge blood pressure transducer and tachograph. ΔV3V microinjections of (2 µl) 1.5 mol/l NaCl solution were done according to brain coordinates: AP = 7.0 mm, L = 1.0 mm, D = 7.5 mm through a 0.2-mm diameter stainless steel needle. The injection site was verified with 1.0 µl neutral red solution. Basal systolic blood pressure increased 37.6 and 39.6 mm Hg after testosterone (1 mg/kg/day for 20 days) and nandrolone (1 mg/kg/day for 20 days) treatment respectively; diastolic blood pressure also increased upon testosterone and nandrolone treatment in 36.4 and 53.1 mm Hg, respectively; basal heart rate did not change. Vasopressor response to 1.5 mol/l NaCl ΔV3V microinjection was higher in testosterone-treated rats; systolic blood pressure increased 56.0 vs. 28.3 control mm Hg; diastolic blood pressure increased 54.0 vs. 25 control mm Hg. This hypertensive response was 29% longer lasting in testosterone compared to vehicle-treated rats. The same pattern of ΔV3V sensitization to hypertonic NaCl was observed in nandrolone-treated rats. Blood lipid profile changed to a proatherogenic fashion upon testosterone and nandrolone long-term treatment; the plasma-free testosterone concentration increased from 4.9 ± 0.9 to 36.0 ±7.1 pg/ml with the same testosterone treatment schedule. In conclusion, long-term androgenic steroid treatment sensitizes the brain ΔV3V region to hypertonic NaCl which in turn conducts into a sympathetic vasopressor and heart rate-stimulating action.

PHARMACOLOGICAL MODULATION OF THE CARDIOVASCULAR RESPONSE TO HYPERTONIC NACL INJECTION IN THE ANTEROVENTRAL AREA OF THE RAT BRAIN THIRD VENTRICLE

The anteroventral area of the rat brain third ventricle (AV3V) was stimulated by stereotaxically placed microinjections (1 microliter) of hypertonic 1.5 mol/l NaCl and the responses of mean arterial pressure (MAP) and heart rate (HR) were recorded. Previous injection of terazosin or propranolol (5.0 micrograms) into AV3V, 15 min before 1.5 mol/l NaCl microinjection, did not alter the cardiovascular response pattern induced by 1.5 mol/l NaCl. Prior AV3V treatment with ketanserin (1.0 microgram) significantly reduced (p < 0.01) the MAP and HR increase induced by 1.0 microliter of 1.5 mol/l NaCl without changing basal cardiovascular parameters. Prior AV3V treatment with losartan (10.0 micrograms) significantly reduced (p < 0.01) the hypertension and tachycardia induced by hypertonic NaCl administration. Thus, AV3V serotonin and angiotensin II-sensitive neurons may exert an excitatory role on blood pressure and HR involved with the sympathetic discharge produced by hypertonic NaCl stimulation.