Hernán Gómez Llambí

Chronic cola drinking induces metabolic and cardiac alterations in rats

AIM To investigate the effects of chronic drinking of cola beverages on metabolic and echocardiographic parameters in rats. METHODS Forty-eight male Wistar rats were divided in 3 groups and allowed to drink regular cola (C), diet cola (L), or tap water (W) ad libitum during 6 mo. After this period, 50% of the animals in each group were euthanized. The remaining rats drank tap water ad libitum for an additional 6 mo and were then sacrificed. Rat weight, food, and beverage consumption were measured regularly. Biochemical, echocardiographic and systolic blood pressure data were obtained at baseline, and at 6 mo (treatment) and 12 mo (washout). A complete histopathology study was performed after sacrifice. RESULTS After 6 mo, C rats had increased body weight (+7%, P < 0.01), increased liquid consumption (+69%, P < 0.001), and decreased food intake (-31%, P < 0.001). C rats showed mild hyperglycemia and hypertriglyceridemia. Normoglycemia (+69%, P < 0.01) and sustained hypertriglyceridemia (+69%, P < 0.01) were observed in C after washout. Both cola beverages induced an increase in left ventricular diastolic diameter (C: +9%, L: +7%, P < 0.05 vs W) and volumes (diastolic C: +26%, L: +22%, P < 0.01 vs W; systolic C: +24%, L: +24%, P < 0.05 vs W) and reduction of relative posterior wall thickness (C: -8%, L: -10%, P < 0.05 vs W). Cardiac output tended to increase (C: +25%, P < 0.05 vs W; L: +17%, not significant vs W). Heart rate was not affected. Pathology findings were scarce, related to aging rather than treatment. CONCLUSION This experimental model may prove useful to investigate the consequences of high consumption of soft drinks.

Cardiorenal Involvement in Metabolic Syndrome Induced by Cola Drinking in Rats: Proinflammatory Cytokines and Impaired Antioxidative Protection.

We report experimental evidence confirming renal histopathology, proinflammatory mediators, and oxidative metabolism induced by cola drinking. Male Wistar rats drank ad libitum regular cola (C, n = 12) or tap water (W, n = 12). Measures. Body weight, nutritional data, plasma glucose, cholesterol fractions, TG, urea, creatinine, coenzyme Q10, SBP, and echocardiograms (0 mo and 6 mo). At 6 months euthanasia was performed. Kidneys were processed for histopathology and immunohistochemistry (semiquantitative). Compared with W, C rats showed (I) overweight (+8%, p < 0.05), hyperglycemia (+11%, p < 0.05), hypertriglyceridemia (2-fold, p < 0.001), higher AIP (2-fold, p < 0.01), and lower Q10 level (−55%, p < 0.05); (II) increased LV diastolic diameter (+9%, p < 0.05) and volume (systolic +24%, p < 0.05), posterior wall thinning (−8%, p < 0.05), and larger cardiac output (+24%, p < 0.05); (III) glomerulosclerosis (+21%, p < 0.05), histopathology (+13%, p < 0.05), higher tubular expression of IL-6 (7-fold, p < 0.001), and TNFα (4-fold, p < 0.001). (IV) Correlations were found for LV dimensions with IL-6 (74%, p < 0.001) and TNFα (52%, p < 0.001) and fully abolished after TG and Q10 control. Chronic cola drinking induced cardiac remodeling associated with increase in proinflammatory cytokines and renal damage. Hypertriglyceridemia and oxidative stress were key factors. Hypertriglyceridemic lipotoxicity in the context of defective antioxidant/anti-inflammatory protection due to low Q10 level might play a key role in cardiorenal disorder induced by chronic cola drinking in rats.

Rosuvastatin increases myocardial microvessels in SHR rats. Role of thioredoxin-1 and peroxiredoxin-2 expression

Fil: Cao, Gabriel Fernando. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Investigaciones Cardiologicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Cardiologicas; Argentina

Carvedilol protects the peritubular capillaries and kidney structure in spontaneously hypertensive rats

Fil: Cao, Gabriel Fernando. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Investigaciones Cardiologicas (i); Argentina

Left ventricular hypertrophy does not prevent heart failure in experimental hypertension

BACKGROUND Left ventricular hypertrophy (LVH) secondary to hypertension has been accepted to prevent heart failure (HF) while paradoxically increasing cardiovascular morbi-mortality. OBJECTIVES To evaluate whether antihypertensive treatment inhibits LVH, restores beta-adrenergic response and affects myocardial oxidative metabolism. METHODS Ninety spontaneously hypertensive rats (SHR) were distributed into groups and treated (mg/kg, p.o.) with: losartan 30 (L), hydralazine 11 (H), rosuvastatin 10 (R), carvedilol 20 (C). Hypertension control group comprised 18 normotensive rats (Wistar-Kyoto, WKY). Following euthanasia at 16months, contractility was measured in 50% of rats (Langendorff system) before and after isoproterenol (Iso) 10-9M, 10-7M and 10-5M stimulation. Left ventricular weight (LVW) was measured in the remaining hearts, and normalized by BW. Expression of thioredoxin 1 (Trx-1), peroxyredoxin 2 (Prx-2), glutaredoxin 3 (Grx-3), caspase-3 and brain natriuretic peptide (BNP) was determined. RESULTS Systolic blood pressure (mmHg): 154±3 (L), 137±1 (H), 190±3 (R)*, 206±3 (SHR)*, 183±1 (C)**, and 141±1 (WKY) (*p<0.05 vs. L, H, WKY, **p<0.05 vs. L, H, WKY, SHR). LVW/BW was higher in SHR and R (p<0.05). Groups SHR, R and C evidenced baseline contractile depression. Response to Iso 10-5M was similar in WKY and L. Expression of Trx-1, Prx-2 and Grx-3 increased in C, H, R and L (p<0.01). CONCLUSIONS Present findings argue against the traditional idea and support that LVH might not be required to prevent HF. Increased expression of thioredoxins by antihypertensive treatment might be involved in protection from HF.

Oxidative Stress and Antioxidants in Experimental Metabolic Syndrome

Metabolic syndrome is a prevalent condition in Western and developing countries (20 to 30 % of adults) that represents a serious public health threat. One of the defects in metabolic syndrome and in its associated diseases such as hypertension, dislipemia, insulin resistance and obesity (mainly visceral), is the increase in general oxidative metabolism with development of oxidative stress. This implies the overproduction (and/or reduced degradation) of reactive oxygen species that usually overrides the physiological antioxidative defense. Thus, there is an increase in the oxidant-to-antioxidant compounds’ ratio. In this chapter, we comment and revise some of our evidence on this topic obtained in an experimental model of metabolic syndrome. In particular, we have found that chronic consumption of cola beverages, either sucrose- or artificially-sweetened cola, leads to a condition that reproduces the typical features of human metabolic syndrome. Following the characterization of our model, we have succeeded in replicating this model as shown in our first studies. Here we share some of the most important findings in relation with oxidative metabolism both general and tisular, with particular emphasis on hypertriglyceridemia, pancreatic and renal changes. Oxidative alterations and inflammatory mechanisms are concurrent in otherwise healthy young adult rats following cola beverage drinking for long periods.