Telmisartan is an angiotensin receptor blocker (ARB) and a selective peroxisome proliferator activated receptor gamma (PPARG) modulator. Recently, we tested metabolic effects of telmisartan (5 mg/kg body weight) in spontaneously hypertensive rats (SHR) fed a diet containing 60 % fructose, a widely used model of the metabolic syndrome. Surprisingly, we observed acute toxic effects of telmisartan. Rats lost body weight rapidly and died within 2 to 3 weeks due to bleeding into the upper gastrointestinal tract. SHR fed a high fructose diet and treated with telmisartan exhibited rapid decrease in blood pressure when compared to the SHR fed a high fructose diet and treated with valsartan. Concentrations of both unconjugated telmisartan and telmisartan glucuronide in the liver of SHR rats fed a high fructose diet were approximately 4 fold higher when compared to Brown Norway (BN) rats fed the same diet. Plasma concentrations of unconjugated telmisartan in the SHR were about 5 fold higher when compared to BN rats while plasma levels of telmisartan glucuronide were similar between the strains. Testing of other rat strains, diets, and the ARB valsartan showed that toxic effects of telmisartan in combination with high fructose diet are specific for the SHR. These results are consistent with the possibility that in some circumstances, SHR are predisposed to telmisartan toxicity possibly because of a genetically determined disturbance in telmisartan metabolism.
Warming winter and atmospheric nitrogen (N) deposition are expected to have effects on net primary production (NPP) of Chinese fir (Cunninghamia lanceolata) plantation and implications for plantation carbon sequestration. The effects of nongrowing-season warming on plant morphological and physiological traits were investigated in a greenhouse experiment with two-year-old C. lanceolata seedlings. Elevated temperature (ET) during the nongrowing season significantly increased the net photosynthetic characteristics. The strongest effects occurred during warming period from 1 December 2014 to 1 February 2015 (W1). Moreover, the carbohydrate concentration was elevated due to the warming during W1, but it declined during four months of the warming (from 1 December 2014 to 1 April 2015, W2). The seedlings kept under N deposition (CN) showed a positive effect in all the above-mentioned parameters except δ13C. Significant interactions between ET and N deposition were observed in most parameters tested. At the end of the experiment (W2), the seedlings exposed to a combined ET and N deposition treatment exhibited the highest carbon contents. Our results showed that N deposition might ameliorate the negative effects of the winter warming on the carbon content., L. Yu, T. F. Dong, Y. B. Lu, M. Y. Song, B. L. Duan., and Obsahuje bibliografii
The aim of this study was to investigate the effect of high fructose intake associated with moderate increase in adiposity on rat arterial adrenergic responses and their modulation by perivascular adipose tissue (PVAT). After eight-week-lasting substitution of drinking water with 10 % fructose solution in adult normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR), their systolic blood pressure, plasma triglycerides, and relative liver weight were elevated when compared to their respective control groups. Moreover, in SHR, body weight and relative heart weight were increased after treatment with fructose. In superior mesenteric arteries, PVAT exerted inhibitory influence on adrenergic contractile
responses and this effect was markedly stronger in control WKY than in SHR. In fructose-administered WKY, arterial adrenergic contractions were substantially reduced in comparison with the control group; this was caused mainly by enhancement of anticontractile action of PVAT. The diminution of the mesenteric arterial contractions was not observed after fructose treatment in SHR. We conclude that the increase in body adiposity due to fructose overfeeding in rats might have prohypertensive effect. However, in WKY it might cause PVAT-dependent and independent reduction in arterial contractile responses to adrenergic stimuli, which could attenuate the pathological elevation in vascular tone.
Metabolic syndrome is a prevalent disease resulting from an interplay of genomic component and the exposome. Parental diet has been shown to affect offspring metabolic health via multiple epigenetic mechanisms. Excess carbohydrate intake is one of the driving forces of the obesity and metabolic syndrome pandemics. This review summarizes the evidence for the effects of maternal carbohydrate (fructose, sucrose, glucose) overnutrition on the modulation of metabolic syndrome components in the offspring. Despite substantial discrepancies in experimental design, common effects of maternal carbohydrate overnutrition include increased body weight and hepatic lipid content of the "programmed" offspring. However, the administration of sucrose to several rat models leads to apparently favorable metabolic outcomes. Moreover, there is evidence for the role of genomic background in modulating the metabolic programming effect in the form of nutri-epigenomic interaction. Comprehensive, robust studies are needed to resolve the temporal, sex-specific, genetic, epigenetic and nutritional aspects of parental overnutrition in the intergenerational and transgenerational pathogenesis of metabolic syndrome.