Age-dependent effect of high-fructose and high-fat diets on lipid metabolism and lipid accumulation in liver and kidney of rats.

Background: The metabolic syndrome (MS) is characterized by variable coexistence of metabolic and pathophysiological alterations which are important risk factors for developing of type II diabetes and/or cardiovascular diseases. Increased of MS patients in worldwide has stimulated the development of experimental models. However, it is still challenging to find an dietetic model that most closely approximates human MS and, in addition, is not yet fully established the effect of different diets of MS in lipid metabolism in rats of different ages. The aim of this study was to evaluate the effect of different diets of MS in lipid metabolism and ectopic fat deposition and define the most appropriate diet for inducing the characteristic disturbances of the human MS in rats of different ages. Methods: Young (4 weeks old) and adult rats (12 weeks old) were given a high-fat (FAT) or high-fructose diet (FRU) for 13 weeks and biochemical, physiological, histological and biometric parameters were evaluated. Results: In young rats, the FAT diet induced increased mean blood pressure (MAP) and heart rate (HR), body weight after 6 to 10 weeks, and in the 13th week, increased the liver, mesenteric, retroperitoneal and epididymal fat weights,fasting glucose, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and reduced HDL cholesterol; and also induced non-alcoholic fatty liver disease (NAFLD) and renal inflammatory infiltrates. In adult rats, the FRU diet induced transient elevations of MAP and HR in the 6th week, and, at 13 weeks, increased fasting glucose, triglycerides, total cholesterol, AST and ALT; increased liver, kidneys and retroperitoneal fat weights; and induced macrovesicular and microvesicular NAFLD, the presence of fat cells in the kidney, glomerular sclerosis, and liver and kidney inflammation. Additionally, the FAT and FRU diets induced, respectively, increases in liver glycogen in adults and young rats. Conclusions: Our data show that FRU diet in adult rats causes biggest change on metabolism of serum lipids and lipid accumulation in liver and kidney, while the FAT diet in young rats induces elevation of MAP and HR and higher increased visceral lipid stores, constituting the best nutritional interventions to induce MS in rats

Hypotensive effect of Ang II and Ang-(1-7) at the caudal ventrolateral medulla involves different mechanisms.

Hypotensive effect of ANG II and ANG-(1?7) at the caudal ventrolateral medulla involves different mechanisms. Am J Physiol Regul Integr Comp Physiol 283: R1187?R1195, 2002. First published July 18, 2002; 10.1152/ ajpregu.00580.2001.?The objective of the present study was to determine the contribution of the autonomic nervous system and nitric oxide to the depressor effect produced by unilateral microinjection of ANG-(1?7) and ANG II into the caudal ventrolateral medulla (CVLM). Unilateral microinjection of ANG-(1?7), ANG II (40 pmol), or saline (100 nl) was made into the CVLM of male Wistar rats anesthetized with urethane before and after intravenous injection of 1) methylatropine, 2.5 mg/kg; 2) prazosin, 25 g/kg; 3) the nitric oxide synthase (NOS) inhibitor, NG-nitro-L-arginine methyl ester (L-NAME), 5 mg/kg; or 4) the specific inhibitor of neuronal NOS, 7-nitroindazole (7-NI), 45 mg/kg. Arterial pressure and heart rate (HR) were continuously monitored. Microinjection of ANG-(1?7) or ANG II into the CVLM produced a significant decrease in mean arterial pressure (MAP; 11 1 mmHg, n 12 and 10 1 mmHg, n 10, respectively) that was not accompanied by consistent changes in HR or in cardiac output. The effect of ANG-(1?7) was abolished after treatment with methyl-atropine ( 3 0.6 mmHg, n 9) or L-NAME ( 2.3 0.5 mmHg, n 8) or 7-NI ( 2.8 0.6 mmHg, n 5). In contrast, these treatments did not significantly interfere with the ANG II effect ( 10 2.6 mmHg, n 8; 8 1.5 mmHg, n 8; and 12 3.6 mmHg, n 6; respectively). Peripheral treatment with prazosin abolished the hypotensive effect of ANG-(1?7) and ANG II. Microinjection of saline did not produce any significant change in MAP or in HR. These results suggest that the hypotensive effect produced by ANG II at the CVLM depends on changes in adrenergic vascular tonus and, more importantly, the hypotensive effect produced by ANG-(1?7) also involves a nitric oxide-related mechanism

Baroreflex modulation by angiotensins at the rat rostral and caudal ventrolateral medulla.

Baroreflex modulation by angiotensins at the rat rostral and caudal ventrolateral medulla. Am J Physiol Regul Integr Comp Physiol 290: R1027?R1034, 2006. First published November 23, 2005; doi:10.1152/ajpregu.00852.2004.?We determined the effect of microinjection of ANG-(1?7) and ANG II into two key regions of the medulla that control the circulation [rostral and caudal ventrolateral medulla (RVLM and CVLM, respectively)] on baroreflex control of heart rate (HR) in anesthetized rats. Reflex bradycardia and tachycardia were induced by increases and decreases in mean arterial pressure produced by intravenous phenylephrine and sodium nitroprusside, respectively. The pressor effects of ANG-(1?7) and ANG II (25 pmol) after RVLM microinjection (11 0.8 and 10 2 mmHg, respectively) were not accompanied by consistent changes in HR. In addition, RVLM microinjection of these angiotensin peptides did not alter the bradycardic or tachycardic component of the baroreflex. CVLM microinjections of ANG-(1?7) and ANG II produced hypotension ( 11 1.5 and 11 1.9 mmHg, respectively) that was similarly not accompanied by significant changes in HR. However, CVLM microinjections of angiotensins induced differential changes in the baroreflex control of HR. ANG-(1?7) attenuated the baroreflex bradycardia (0.26 0.06 ms/mmHg vs. 0.42 0.08 ms/mmHg before treatment) and facilitated the baroreflex tachycardia (0.86 0.19 ms/mmHg vs. 0.42 0.10 ms/mmHg before treatment); ANG II produced the opposite effect, attenuating baroreflex tachycardia (0.09 0.06 ms/mmHg vs. 0.31 0.07 ms/mmHg before treatment) and facilitating the baroreflex bradycardia (0.67 0.16 ms/mmHg vs. 0.41 0.05 ms/mmHg before treatment). The modulatory effect of ANG II and ANG-(1?7) on baroreflex sensitivity was completely abolished by peripheral administration of methylatropine. These results suggest that ANG II and ANG-(1?7) at the CVLM produce a differential modulation of the baroreflex control of HR, probably through distinct effects on the parasympathetic drive to the heart

Hemodynamic effect produced by microinjection of angiotensins at the caudal ventrolateral medulla of spontaneously hypertensive rats.

In the present study, the effect of caudal ventro-lateral medulla (CVLM) microinjection of angiotensin-(1-7) (Ang-(1-7)) and angiotensin II (Ang II) on mean arterial pres-sure (MAP), heart rate (HR) and pulsatile vascular blood flow (VBF; Transonic System) of the femoral, renal or mesenteric arteries was evaluated in male Wistar and spontaneously hypertensive rats (SHR) anesthetized with urethane. The vas-cular resistance (VR) was calculated by the ratio between the changes in MAP and VBF. Ang-(1-7) (40 ng) and Ang II (40 ng) microinjection into the CVLM caused similar depressor ef-fects in Wistar rats and SHR. The hypotensive effect pro-duced by Ang-(1-7) into the CVLM of Wistar rats was accom-panied by a decrease in femoral ( VR/VRbaseline 0.12 0.04 vs. 0.001 0.03; after saline) and renal ( VR/VRbase-line 0.10 0.02 vs. 0.003 0.02; after saline) vascular re-sistance. On the other hand, the Ang II hypotensive effect in Wistar rats produced only changes in renal vascular resis-tance ( VR/VRbaseline 0.16 0.02 vs. 0.003 0.02; after saline). In SHR, the hypotensive effect produced by Ang-(1-7) and Ang II caused decrease in renal vascular resistance ( VR/VRbaseline 0.18 0.03 and 0.13 0.01, respectively, as compared with saline, VR/VRbaseline 0.06 0.02), but did not alter the femoral or mesenteric vascular resistance. These data show that Ang II and Ang-(1-7) hypotensive effect at the CVLM involves the participation of different vascular beds. Further, the lack of involvement of the femoral vascular bed in SHR suggests that hypertension may induce alteration in the neural control of the different vascular beds, at least at the CVLM

Hypotensive effect induced by microinjection of Alamandine, a derivative of angiotensin-(1?7), into caudal ventrolateral medulla of 2K1C hypertensive rats.

In the present study we evaluated the cardiovascular effects produced by microinjection of the new component of the renin-angiotensin system, alamandine, into caudal ventrolateral medulla of urethane-anesthetized normotensive and hypertensive 2K1C rats. The participation of different angiotensin receptors in the effects of alamandine was also evaluated. Microinjection of angiotensin-(1?7) was used for comparison. The microinjection of 4, 40 and 140 pmol of alamandine or angiotensin-(1?7) into caudal ventrolateral medulla induced similar hypotensive effects in Sham-operated rats. However, contrasting with angiotensin-(1?7), in 2K1C rats the MAP response to the highest dose of alamandine was similar to that observed with saline. The microinjection of A- 779, a selective Mas receptor antagonist, blunted the angiotensin-(1?7) effects but did not block the hypotensive effect of alamandine in Sham or in 2K1C rats. However, microinjection of D-Pro7-angiotensin-(1?7), a Mas/MrgD receptor antagonist, blocked the hypotensive effect induced by both peptides. Furthermore, microinjection of PD123319, a putative AT2 receptor antagonist blocked the hypotensive effect of alamandine, but not of angiotensin-( 1?7), in Sham and 2K1C rats. Microinjection of the AT1 receptor antagonist, losartan, did not alter the hypotensive effect of angiotensin-(1?7) or alamandine in both groups. These results provide new insights about the differential mechanisms participating in the central cardiovascular effects of alamandine and angiotensin- (1?7) in normotensive and 2K1C hypertensive rats

Differential control of vasomotion by angiotensins in the rostral ventrolateral medulla of hypertensive rats.

The central and peripheral renin?angiotensin systems are known for playing a key role in cardiovascular control. In the present study,we evaluated the hemodynamic effects produced by nanoinjections of angiotensin II (Ang II) or angiotensin-(1?7) [Ang-(1?7)] into the rostral ventrolateral medulla (RVLM) of adult male normotensive (Wistar?WT) and spontaneously hypertensive rats (SHR). Animals were anesthetized (urethane 1.2 g/kg) and instrumented for recording blood pressure (BP), heart rate (HR) and blood flow (BF) in the femoral, renal or mesenteric arteries. Afterwards, rats were positioned in a stereotaxic and prepared for nanoinjections (100 nl) of saline (NaCl 0.9%), Ang-(1?7) (40 ng) or Ang II (40 ng) into the RVLM. The vascular resistance (VR)was calculated by ?MAP/?BF ratio. In WT, Ang-(1?7) or Ang II caused equipotent pressor effects that were not accompanied by changes in vascular resistance. However, MAP changes were greater in SHR. This strain also showed a concomitant increase in relative vascular resistance (?VR/VRbaseline) of renal (0.31 ? 0.07 and 0.3 ? 0.07 vs. 0.02 ? 0.01; Ang-(1?7), Ang II and Saline, respectively) and mesenteric beds (0.3 ? 0.06 and 0.33 ? 0.04 vs. 0.05 ? 0.02; Ang-(1?7), Ang II and saline, respectively). We conclude that Ang II and Ang-(1?7) at the RVLM control the vascular resistance of renal and mesenteric beds during hypertension

The ACE2/Angiotensin-(1-7)/MAS axis of the renin-angiotensin system : focus on Angiotensin-(1-7).

The renin-angiotensin system (RAS) is a key player in the control of the cardiovascular system and hydroelectrolyte balance, with an influence on organs and functions throughout the body. The classical view of this system saw it as a sequence of many enzymatic steps that culminate in the production of a single biologically active metabolite, the octapeptide angiotensin (ANG) II, by the angiotensin converting enzyme (ACE). The past two decades have revealed new functions for some of the intermediate products, beyond their roles as substrates along the classical route. They may be processed in alternative ways by enzymes such as the ACE homolog ACE2. One effect is to establish a second axis through ACE2/ANG-(1?7)/MAS, whose end point is the metabolite ANG- (1?7). ACE2 and other enzymes can form ANG-(1?7) directly or indirectly from either the decapeptide ANG I or from ANG II. In many cases, this second axis appears to counteract or modulate the effects of the classical axis. ANG-(1?7) itself acts on the receptor MAS to influence a range of mechanisms in the heart, kidney, brain, and other tissues. This review highlights the current knowledge about the roles of ANG-(1?7) in physiology and disease, with particular emphasis on the brain

Physical training improves thermogenesis and insulin pathway, and induces remodeling in white and brown adipose tissues.

Physical training (PT) has been considered as a treatment in metabolic syndrome (MS), since it induces thermogenic activity in brown (BAT) and white (WAT) adipose tissues. We evaluated the therapeutic effect of PT on activity of WAT and BAT in rats with MS induced by high-fat diet (30% lard) for 13 weeks and submitted, for the last 6 weeks, to swimming or kept sedentary (SED) rats. MS-SED rats compared to control diet (CT-SED) rats showed low physical fitness and high levels of glucose, insulin, homeostasis evaluation of insulin resistance (HOMA-IR), homeostasis evaluation of the functional capacity of ?-cells (HOMA-?), and blood pressure. The gastrocnemius muscle decreased in peroxisome proliferator-activated receptor gamma coactivator 1-alpha and beta (PGC-1?, PGC-1?), and uncoupled protein 2 and 3 (UCP2 and UCP3) expressions. Both WAT and BAT increased in the adipocyte area and decreased in blood vessels and fibroblast numbers. WAT increased in expression of pro-inflammatory adipokines and decreased in anti-inflammatory adipokine and adiponectin. WAT and gastrocnemius showed impairment in the insulin signaling pathway. In response to PT, MS rats showed increased physical fitness and restoration of certain biometric and biochemical parameters and blood pressure. PT also induced thermogenic modulations in skeletal muscle, WAT and BAT, and also improved the insulin signaling pathway. Collectively, PT was effective in treating MS by inducing improvement in physical fitness and interchangeable effects between skeletal muscle, WAT and BAT, suggesting a development of brown-like adipocyte cells

Lifetime overproduction of circulating angiotensin?(1?7) in rats attenuates the increase in skeletal muscle damage biomarkers after exhaustive exercise.

Angiotensin?(1?7) (Ang?[1?7]) can modulate glucose metabolism and protect against muscular damage. The aim of this study was to investigate the influence of lifetime increase of circulating levels of Ang?(1?7) at exhaustive swimming exercise (ESE). Sprague?Dawley (SD) and transgenic rats TGR(A1?7)3292 (TR) which overproduce Ang?(1?7) (2.5?fold increase) were submitted to ESE. The data showed no differences in time to exhaustion (SD: 4.90 ? 1.37 h vs. TR: 5.15 ? 1.15 h), creatine kinase, and transforming growth factor beta (TGF-?). Lactate dehydrogenase (SD: 219.9 ? 12.04 U/L vs. TR: 143.9 ? 35.21 U/L) and ??actinin (SD: 336.7 ? 104.5 U/L vs. TR: 224.6 ? 82.45 U/L) values were significantly lower in TR. There was a significant decrease in the range of blood glucose levels (SD: ?41.4 ? 28.32 mg/dl vs. TR: ?13.08 ? 39.63 mg/dl) in SD rats. Muscle (SD: 0.06 ? 0.02 mg/g vs. TR: 0.13 ? 0.01 mg/g) and hepatic glycogen (SD: 0.66 ? 0.36 mg/g vs. TG: 2.24 ? 1.85 mg/g) in TR were higher. The TR presented attenuation of the increase in skeletal muscle damage biomarkers and of the changes in glucose metabolism after ESE

Time-course effects of aerobic exercise training on cardiovascular and renal parameters in 2K1C renovascular hypertensive rats.

Exercise training (Ex) has been recommended for its beneficial effects in hypertensive states. The present study evaluated the time-course effects of Ex without workload on mean arterial pressure (MAP), reflex bradycardia, cardiac and renal histology, and oxidative stress in two-kidney, one-clip (2K1C) hypertensive rats. Male Fischer rats (10 weeks old; 150?180 g) underwent surgery (2K1C or SHAM) and were subsequently divided into a sedentary (SED) group and Ex group (swimming 1 h/day, 5 days/week for 2, 4, 6, 8, or 10 weeks). Until week 4, Ex decreased MAP, increased reflex bradycardia, prevented concentric hypertrophy, reduced collagen deposition in the myocardium and kidneys, decreased the level of thiobarbituric acid-reactive substances (TBARS) in the left ventricle, and increased the catalase (CAT) activity in the left ventricle and both kidneys. From week 6 to week 10, however, MAP and reflex bradycardia in 2K1C Ex rats became similar to those in 2K1C SED rats. Ex effectively reduced heart rate and prevented collagen deposition in the heart and both kidneys up to week 10, and restored the level of TBARS in the left ventricle and clipped kidney and the CAT activity in both kidneys until week 8. Ex without workload for 10 weeks in 2K1C rats provided distinct beneficial effects. The early effects of Ex on cardiovascular function included reversing MAP and reflex bradycardia. The later effects of Ex included preventing structural alterations in the heart and kidney by decreasing oxidative stress and reducing injuries in these organs during hypertension