Nutritional disorders during the perinatal period cause cardiometabolic dysfunction, which is observable in the early overfeeding (EO) experimental model. Therefore, severe caloric restriction has the potential of affecting homeostasis through the same epigenetic mechanisms, and its effects need elucidation. This work aims to determine the impact of food restriction (FR) during puberty in early overfed obese and non-obese animals in adult life. Three days after delivery (PN3), Wistar rats were separated into two groups: normal litter (NL; 9 pups) and small litter (SL; 3 pups). At PN30, some offspring were subjected to FR (50%) until PN60, or maintained with free access to standard chow. NL and SL animals submitted to food restriction (NLFR and SLFR groups) were kept in recovery with free access to standard chow from PN60 until PN120. Body weight and food intake were monitored throughout the experimental period. At PN120 cardiovascular parameters were analyzed and the animals were euthanized for sample collection. SLNF and SLFR offspring were overweight and had increased adiposity. Differences in blood pressure were observed only between obese and non-obese animals. Obese and FR animals have cardiac remodeling showing cardiomyocyte hypertrophy and the presence of interstitial and perivascular fibrosis. FR animals also show increased expression of AT1 and AT2 receptors and of total ERK and p-ERK. The present study showed that EO leads to the obese phenotype and cardiovascular disruptions. Interestingly, we demonstrated that severe FR during puberty leads to cardiac remodeling.

Modern lifestyle increases the prevalence of obesity and its co-morbidities in the young population. High-salt (HS) diets are associated with hypertension and cardiac remodelling. The present study evaluated the potential effects of cardiometabolic programming induced by HS intake during puberty in lean and obese rats. Additionally, we investigated whether HS could exacerbate the impairment of cardiovascular parameters in adult life due to postnatal early overnutrition (PO). At postnatal day 3 (PN3), twenty-four litters of Wistar rats were divided into two groups: normal litter (NL, nine pups/dam) and small litter (SL, three pups/dam) throughout the lactation period; weaning was at PN21. At PN30, the pups were subdivided into two more groups: NL plus HS (NLHS) and SL plus HS (SLHS). HS intake was from PN30 until PN60. Cardiovascular parameters were evaluated at PN120. SL rats became overweight at adulthood due to persistent hyperphagia; however, HS exposure during puberty reduced the weight gain and food intake of NLHS and SLHS. Both HS and obesity raised the blood pressure, impaired baro- and chemoreflex sensitivity and induced cardiac remodelling but no worsening was observed in the association of these factors, except a little reduction in the angiotensin type-2 receptor in the hearts from SLHS animals. Our results suggest that the response of newborn offspring to PO and juveniles to a HS diet leads to significant changes in cardiovascular parameters in adult rats. This damage may be accompanied by impairment of both angiotensin signalling and antioxidant defence in the heart.

Agents that block the renin–angiotensin system (RAS) improve glucoregulation in the metabolic syndrome disorder. We evaluated the effects of egg white hydrolysate (EWH), previously shown to modulate the protein abundance of RAS component in vivo, on glucose homeostasis in diet-induced insulin-resistant rats. Sprague–Dawley rats were fed a high-fat diet (HFD) for 6 weeks to induce insulin resistance. They were then randomly divided into four groups receiving HFD or HFD supplemented with different concentrations of EWH (1, 2 and 4 %) for another 6 weeks in the first trial. In the second trial, insulin-resistant rats were divided into two groups receiving only HFD or HFD+4 % EWH for 6 weeks. Glucose homeostasis was assessed by oral glucose tolerance and insulin tolerance tests. Insulin signalling and protein abundance of RAS components, gluconeogenesis enzymes and PPARγ were evaluated in muscle, fat and liver. Adipocyte morphology and inflammatory markers were evaluated. In vivo administration of EWH increased insulin sensitivity, improved oral glucose tolerance (P < 0·0001) and reduced systemic inflammation (P < 0·05). EWH potentiated insulin-induced Akt phosphorylation in muscle (P = 0·0341) and adipose tissue (P = 0·0276), but minimal differences in the protein abundance of tissue RAS components between the EWH and control groups were observed. EWH treatment also reduced adipocyte size (P = 0·0383) and increased PPARγ2 protein abundance (P = 0·0237). EWH treatment yielded positive effects on the inflammatory profile, glucose tolerance, insulin sensitivity and adipocyte differentiation in HFD-induced insulin resistance rats. The involvement of local RAS activity requires further investigation.

Previous studies have shown that the renin–angiotensin system (RAS) is affected by adverse maternal nutrition during pregnancy. The aim of this study was to investigate the effects of a maternal low-protein diet on proinflammatory cytokines, reactive oxygen species and RAS components in kidney samples isolated from adult male offspring. We hypothesized that post-weaning losartan treatment would have beneficial effects on RAS activity and inflammatory and oxidative stress markers in these animals. Pregnant Sprague–Dawley rats were fed with a control (20% casein) or low-protein diet (LP) (6% casein) throughout gestation. After weaning, the LP pups were randomly assigned to LP and LP-losartan groups (AT1 receptor blockade: 10 mg/kg/day until 20 weeks of age). At 20 weeks of age, blood pressure levels were higher and renal RAS was activated in the LP group. We also observed several adverse effects in the kidneys of the LP group, including a higher number of CD3, CD68 and proliferating cell nuclear antigen-positive cells and higher levels of collagen and reactive oxygen species in the kidney. Further, our results revealed that post-weaning losartan treatment completely abolished immune cell infiltration and intrarenal RAS activation in the kidneys of LP rats. The prevention of augmentation of angiotensin (Ang II) concentration abolished inflammatory and fibrotic events, indicating that Ang II via the AT1 receptor is essential for pathological initiation. Our results suggest that the prenatal programming of hypertension is dependent on the up-regulation of local RAS and presence of immune cells in the kidney.

CVD are the leading cause of death in women globally, with ageing associated with progressive endothelial dysfunction and increased CVD risk. Natural menopause is characterised by raised non-fasting TAG concentrations and impairment of vascular function compared with premenopausal women. However, the mechanisms underlying the increased CVD risk after women have transitioned through the menopause are unclear. Dietary fat is an important modifiable risk factor relating to both postprandial lipaemia and vascular reactivity. Meals rich in SFA and MUFA are often associated with greater postprandial TAG responses compared with those containing n-6 PUFA, but studies comparing their effects on vascular function during the postprandial phase are limited, particularly in postmenopausal women. The present review aimed to evaluate the acute effects of test meals rich in SFA, MUFA and n-6 PUFA on postprandial lipaemia, vascular reactivity and other CVD risk factors in postmenopausal women. The systematic search of the literature identified 778 publications. The impact of fat-rich meals on postprandial lipaemia was reported in seven relevant studies, of which meal fat composition was compared in one study described in three papers. An additional study determined the impact of a high-fat meal on vascular reactivity. Although moderately consistent evidence suggests detrimental effects of high-fat meals on postprandial lipaemia in postmenopausal (than premenopausal) women, there is insufficient evidence to establish the impact of meals of differing fat composition. Furthermore, there is no robust evidence to conclude the effect of meal fatty acids on vascular function or blood pressure. In conclusion, there is an urgent requirement for suitably powered robust randomised controlled trials to investigate the impact of meal fat composition on postprandial novel and established CVD risk markers in postmenopausal women, an understudied population at increased cardiometabolic risk.

Low-protein diet plus ketoacids (LPD+KA) has been reported to decrease proteinuria in patients with chronic kidney diseases (CKD). However, the mechanisms have not been clarified. As over-activation of intrarenal renin–angiotensin system (RAS) has been shown to play a key role in the progression of CKD, the current study was performed to investigate the direct effects of LPD+KA on intrarenal RAS, independently of renal haemodynamics. In this study, 3/4 subtotal renal ablated rats were fed 18 % normal-protein diet (Nx-NPD), 6 % low-protein diet (Nx-LPD) or 5 % low-protein diet plus 1 % ketoacids (Nx-LPD+KA) for 12 weeks. Sham-operated rats fed NPD served as controls. The level of proteinuria and expression of renin, angiotensin II (AngII) and its type 1 receptors (AT1R) in the renal cortex were markedly higher in Nx-NPD group than in the sham group. LPD+KA significantly decreased the proteinuria and inhibited intrarenal RAS activation. To exclude renal haemodynamic impact on intrarenal RAS, the serum samples derived from the different groups were added to the culture medium of mesangial cells. It showed that the serum from Nx-NPD directly induced higher expression of AngII, AT1R, fibronectin and transforming growth factor-β1 in the mesangial cells than in the control group. Nx-LPD+KA serum significantly inhibited these abnormalities. Then, proteomics and biochemical detection suggested that the mechanisms underlying these beneficial effects of LPD+KA might be amelioration of the nutritional metabolic disorders and oxidative stress. In conclusion, LPD+KA could directly inhibit the intrarenal RAS activation, independently of renal haemodynamics, thus attenuating the proteinuria in CKD rats.

Renin is essential for renal development and in adult kidneys vitamin D deficiency increases renin gene expression. We aimed to determine whether maternal vitamin D deficiency upregulates fetal renal renin expression, and if this is sustained. We also examined growth and the long-term renal effects in offspring on a normal diet. Female Sprague–Dawley rats in UVB-free housing were fed either vitamin D deficient chow (DEF) or normal chow from 4 weeks and mated with vitamin D replete males at 10 weeks. Fetuses were collected at E20 or dams littered and the pups were weaned onto normal chow. Kidney mRNA levels for renin, (pro)renin receptor [(P)RR], transforming growth factor β 1 (TGF-β1), and nephrin were determined in E20 fetuses and in male offspring at 38 weeks. Renal function was assessed at 33 weeks (24 h, metabolic cage) in both sexes. Renal mRNA expression was upregulated for renin in fetuses (P < 0.05) and was almost doubled in adult male offspring from DEF dams (P < 0.05). Adult males had reduced creatinine clearance, solute excretion and a suppressed urinary sodium-to-potassium ratio (P < 0.05). Female adult DEF offspring drank more and excreted more urine (P < 0.05) but creatinine clearance was not impaired. We conclude that maternal vitamin D depletion upregulates fetal renal renin gene expression and this persists into adulthood where, in males only, there is evidence of sodium retention and compromised renal function. Importantly these effects occurred despite the animals being on a normal diet from the time of weaning onwards.

Abdominal obesity is a risk factor for cardiovascular disease worldwide, and it is becoming a dramatic issue for national health systems. Overweight and obesity are highly associated with multiple comorbidities, elevated blood pressure values, dyslipidaemia, reduced insulin sensitivity and alterations of large and minor vessels.

Activation of the renin–angiotensin system (RAS) in adipose tissue may represent an important link between obesity and hypertension. Angiotensin II has been shown to play a role in adipocyte growth and differentiation. Adipocytes also secrete adiponectin, enhancing insulin sensitivity and preventing atherosclerosis. Blockade of the RAS with either an angiotensin-converting enzyme inhibitor or an angiotensin II receptor blocker results in a substantial increase in adiponectin levels and improved insulin sensitivity. Obesity-related hypertension needs a comprehensive approach to treatment including both weight loss and pharmacological therapies. Antihypertensive drugs prescription should be based on guidelines recommendations for management of hypertension, taking into account the growing evidences about the relationship between some antihypertensive drugs and the development of new-onset diabetes.

This review discusses the role of RAS in the relationship between obesity, essential hypertension and insulin resistance.

Summary

Background and objective: The aim of this study was to investigate the effect of ketamine on the endocrine and lipid metabolic status of the renal-banded animals. Methods: Forty male rats were randomly divided into four groups. Group A served as control, Group B animals received ketamine intraperitoneally at a dose of 100 mg kg−1, Group C was submitted to 2-kidney 1-clip experimental hypertension and Group D received ketamine as above, as well as being submitted to renal artery clipping. Atrial natriuretic peptide, angiotensin II and free fatty acid concentrations were measured in serum. In addition, adipose tissue lipoprotein lipase activity and angiotensin II content were determined, while the left ventricular weight relative to body weight was used as a cardiac hypertrophy index. Results: In renal-banded rats (Groups C and D) serum atrial natriuretic peptide, free fatty acid and angiotensin II concentrations as well as ventricular weight were increased, while adipose tissue lipoprotein lipase activity was lower than in control animals (Groups A and B). Ketamine administration did not influence angiotensin II concentrations either in normal (Group B) or banded rats (Group D). Ketamine increased serum atrial natriuretic peptide and free fatty acid concentrations only in normal animals (Group B). It had no influence on adipose tissue lipoprotein lipase activity either in normal (Group B) or banded animals (Group D). Adipose angiotensin II content did not differ between the four groups. Conclusion: Ketamine increased the atrial natriuretic peptide and free fatty acid concentration in normal rats. In 2-kidney 1-clip animals, ketamine did not elicit an additional response of serum atrial natriuretic peptide or free fatty acids levels. Its contribution to these factors was not significant.

Summary

Background and objective: We have investigated the concentrations of epinephrine, norepinephrine, vasopressin and angiotensin converting enzyme activity to explore the role of these mediators in the neuroendocrine response to laryngoscopy and tracheal intubation. Methods: One hundred (50 male, 50 female) ASA I patients aged 20–50 yr (mean ± SEM; 35.59 ± 0.99) were included in the study. They were undergoing elective surgery under standard anaesthesia induction and maintenance using tracheal intubation. Plasma concentrations of epinephrine, norepinephrine and vasopressin as well as plasma angiotensin converting enzyme activity were determined at four time points, before (T1) and after (T2) induction, and 2 (T3) and 5 min (T4) after intubation. Blood pressure and heart rate were recorded at corresponding times to reveal if any correlation existed between haemodynamic parameters and neuroendocrine response. Results: Heart rate increased after induction and intubation (P < 0.05) and decreased significantly at T4 (P < 0.05). Systolic blood pressure decreased significantly (P < 0.05) after induction and increased slightly after intubation decreasing to below baseline value (P < 0.05) at T4. Diastolic blood pressure increased slightly after intubation and decreased significantly (P < 0.05) at T4. Plasma epinephrine and norepinephrine concentrations decreased after induction and increased at T3 and T4 without reaching significance. Vasopressin concentrations increased slightly at T2 and T3 and decreased significantly at T4 (P < 0.05). Angiotensin converting enzyme activity was unaffected when compared with baseline values. Conclusions: Blood pressure, heart rate, plasma epinephrine, norepinephrine and vasopressin concentrations increased slightly in response to laryngoscopy and intubation, all returning to or below baseline 5 min later with no change in angiotensin converting enzyme activity in normotensive patients.

Summary

Background and objective: This study was undertaken to investigate the role played by antidiuretic hormone (ADH), the renin–angiotensin system and atrial natriuretic factor (ANF) in the oliguria in patients undergoing spinal fusion.

Methods: Sixteen patients undergoing posterior spinal fusion using isoflurane and fentanyl (n = 8) or sufentanil (n = 8) had renin, aldosterone, ADH and ANF measurements.

Results: Compared to the non-oliguric patients, the oliguric patients had a higher number of fused vertebrae 10.5 ± 1.3 vs. 9.0 ± 0.5 (P = 0.01) and higher renin values at 12 h (3.3 ± 3.2 vs. 0.7 ± 0.6 ng L−1 s−1, P = 0.04). Hormonal values that had a significant correlation with intraoperative diuresis were: renin at 0.5 h (r2 = 0.26, P = 0.04), aldosterone at 0.5 h (r2 = 0.30, P = 0.03) and ANF at 0.5 h (r2 = 0.32, P = 0.02). Those that had a significant correlation with the mean postoperative diuresis were: renin at 6 h (r2 = 0.29, P = 0.03), 8 h (r2 = 0.26, P = 0.04) and 12 h (r2 = 0.31, P = 0.03), aldosterone at 6 h (r2 = 0.54, P = 0.001), 8 h (r2 = 0.40, P = 0.01) and 12 h (r2 = 0.32, P = 0.03), ADH at 24 h (r2 = 0.38, P = 0.01) and ANF at 6 h (r2 = 0.26, P = 0.045). Using stepwise regression, excluding hormonal values, only two continuous variables had a significant correlation with the mean postoperative diuresis: the number of fused vertebrae (P = 0.02) and the length of surgery (P = 0.02).

Conclusion: Activation of the renin–angiotensin system is the major cause of the early intraoperative oliguria. ADH and the renin–angiotensin system are both involved in the pathophysiology of postoperative oliguria in patients undergoing spinal fusion.