The usefulness of short-term high-fat/high salt diet as a model of metabolic syndrome in mice.

Diabetic cardiomyopathy (DC) describes diabetes-associated changes in the structure and function of myocardium that are not directly linked to other factors such as hypertension. Currently there are some models of DC; however, they take a large time period to mimic key features. In the present study, we investigated the effects of a short-term high-fat/high salt diet (HFHS) treatment on myocardial function and structure, and vascular reactivity in C57BL/6 male mice. After 14 weeks HFHS induced hypertension (MAP = 144.95 ±â€¯16.13 vs 92.90 ±â€¯18.95 mm Hg), low glucose tolerance (AUC = 1049.01 ±â€¯74.79 vs 710.50 ±â€¯52.57 a.u.), decreased insulin sensitivity (AUC = 429.83 ±â€¯35.22 vs 313.67 ±â€¯19.55 a.u.) and increased adiposity (epididymal fat weight 0.96 ±â€¯0.10 vs 0.59 ±â€¯0.06 OW/BW × 102), aspects present in metabolic syndrome. Cardiac evaluation showed diastolic dysfunction (E/A ratio = 1.20 vs 1.90 u.a.) and cardiomyocyte hypertrophy (cardiomyocyte area = 502.82 ±â€¯31.46 vs 385.58 ±â€¯22.11 µm2). Lastly, vascular reactivity was impaired with higher contractile response (136.10 ±â€¯3.49 vs 120.37 ±â€¯5.43%) and lower response to endothelium-dependent vasorelaxation (74.01 ±â€¯4.35 vs 104.84 ±â€¯3.57%). In addition, the diet was able to induce an inward coronary remodeling (vascular total area: SCNS 6185 ±â€¯800.6 vs HFHS 4085 ±â€¯213.7 µm2). Therefore, we conclude that HFHS short-term treatment was able to induce metabolic syndrome-like state, cardiomyopathy and vascular injury working as an important tool to study cardiometabolic diseases.

Effect of maternal dyslipidaemia on the cardiorespiratory physiology and biochemical parameters in male rat offspring.

The present study evaluated the effects of maternal dyslipidaemia on blood pressure (BP), cardiorespiratory physiology and biochemical parameters in male offspring. Wistar rat dams were fed either a control (CTL) or a dyslipidaemic (DLP) diet during pregnancy and lactation. After weaning, both CTL and DLP offspring received standard diet. On the 30th and 90th day of life, blood samples were collected for metabolic analyses. Direct measurements of BP, respiratory frequency (RF), tidal volume (VT) and ventilation (VE) under baseline condition, as well as during hypercapnia (7 % CO2) and hypoxia (KCN, 0·04 %), were recorded from awake 90-d-old male offspring. DLP dams exhibited raised serum levels of total cholesterol (TC) (4·0-fold), TAG (2·0-fold), VLDL+LDL (7·7-fold) and reduced HDL-cholesterol (2·4-fold), insulin resistance and hepatic steatosis at the end of lactation. At 30 d of age, the DLP offspring showed an increase in the serum levels of TC (P<0·05) and VLDL+LDL (P<0·05) in comparison with CTL offspring. At 90 d of age, DLP offspring exhibited higher mean arterial pressure (MAP, approximately 34 %). In the spectral analysis, the DLP group showed augmented low-frequency (LF) power and LF:high-frequency (HF) ratio when compared with CTL offspring. In addition, the DLP animals showed a larger delta variation in arterial pressure after administration of the ganglionic blocker (P=0·0003). We also found that cardiorespiratory response to hypercapnia and hypoxia was augmented in DLP offspring. In conclusion, the present data show that maternal dyslipidaemia alters cardiorespiratory physiology and may be a predisposing factor for hypertension at adulthood.

Secondary metabolites from Sida rhombifolia L. (Malvaceae) and the vasorelaxant activity of cryptolepinone.

The phytochemical study of Sida rhombifolia L. (Malvaceae) led to the isolation through chromatographic techniques of eleven secondary metabolites: sitosterol (1a) and stigmasterol (1b), sitosterol-3-O-b-D-glucopyranoside (2a) and stigmasterol-3-O-b-D-glucopyranoside (2b), phaeophytin A (3), 17³-ethoxypheophorbide A (4), 13²-hydroxy phaeophytin B (5), 17³-ethoxypheophorbide B (6), 5,7-dihydroxy-4'-methoxyflavone (7), cryptolepinone (8) and a salt of cryptolepine (9). Their structures were identified by ¹H- and ¹³C-NMR using one- and two-dimensional techniques. In addition, the vasorelaxant activity of cryptolepinone in rat mesenteric artery rings is reported herein for the first time.

Central antioxidant therapy inhibits parasympathetic baroreflex control in conscious rats.

Baroreceptor reflex is an important system for neural control of blood pressure. Recently, reactive oxygen species (ROS) have been shown to play an important role in neuronal activity of central areas related to blood pressure control. The aim of this study was to investigate the effects elicited by ascorbic acid (AAC) and N-acetylcysteine (NAC) injections into the 4thV on the parasympathetic component of the baroreflex. Male Wistar rats were implanted with a stainless steel guide cannula into the 4thV. One day prior to the experiments, the femoral artery and vein were cannulated for pulsatile arterial pressure, mean arterial pressure and heart rate measurements and drug administration, respectively. After baseline recordings, the baroreflex was tested with a pressor dose of phenylephrine (PHE, 3 µg/kg, i.v.) and a depressor dose of sodium nitroprusside (SNP, 30 µg/kg, i.v.) before (control) and 5, 15, 30 and 60 min after AAC or NAC into the 4thV. Control PHE injection induced baroreflex-mediated bradycardia (-93 ± 13 bpm, n=7). Interestingly, after AAC injection into the 4thV, PHE injection produced a transient tachycardia at 5 (40 ± 23 bpm), 15 (26 ± 22 bpm) and 30 min (59 ± 21 bpm). No changes were observed in baroreflex-mediated tachycardia evoked by SNP after AAC injection on 4thV (control: 151 ± 23bpm vs. 135 ± 18 bpm at 5 min after AAC, n=7). In the NAC treated group, PHE induced a reduction in reflex bradycardia at 5 min when compared to control (-11 ± 17 bpm vs. -83 ± 15 bpm, n=7). No changes were observed in baroreflex-mediated tachycardia evoked by SNP after NAC injection on 4thV. The antioxidants AAC and NAC may act in the central nervous system affecting the parasympathetic component of the cardiac baroreflex.