The purpose of the present study was to examine the role of the T-786C endothelial nitric oxide synthase (eNOS) gene polymorphism on changes in renal hemodynamics and blood pressure due to Na+ loading. Twenty-eight older (63±1 years), moderately obese (39±2 % fat) hypertensives had th eir glomerular filtration rate (GFR), renal plasma flow (RPF), blood pressure (BP) and plasma nitric oxide (NOx) levels determined after eight days of low (20 mEq) and high (200 mEq) Na+ diets. The two Na+ diets were separated by a 1-week washout period. Subjects were genotyped for the eNOS-786 site and were grouped on whether they were homozygous or heterozygous for the C allele (TC+CC, n=13) or only homozygous for the T allele (TT, n=15). The TC+CC genotype group had a significantly greater increase in diastolic (P=0.021) and mean arterial (P=0.018) BP and a significant decline in both RPF (P=0.007) and GFR (P=0.029) compared to the TT genotype group with Na+ loading. Furthermore, Na+ loading resulted in a significant (P=0.036) increase in plasma NOx in the TT, but not in the TC+CC genotype group as well as a trend (P=0.051) for an increase in urine NOx in TC+CC, but not in the TT genotype group. The increase in BP during Na+ loading in older hypertensives was associated with the eNOS genotype and may be related to changes in renal hemodynamics due to changes in NO metabolism., D. R. Dengel, M. D. Brown, R. E. Ferrell, T. H. Reynolds, M. A. Supiano., and Obsahuje bibliografii a bibliografické odkazy
AMP -activated protein kinase (AMPK) plays a role in metabolic regulation under stress conditions, and inadequate AMPK signaling may be also involved in aging process. The aim was to find out whether AMPK α 2-subunit deletion affects heart function and ische mic tolerance of adult and aged mice. AMPK α 2 -/- (KO) and wild type (WT) female mice were compared at the age of 6 and 18 months. KO mice exhibited subtle myocardial AMPK α 2-subunit protein level, but no difference in AMPK α 1-subunit was detected between the strains. Both α 1- and α 2-subunits of AMPK and their phosphorylation decreased with advanced age. Left ventricular fractional shortening was lower in KO than in WT mice of both age groups and this difference was maintained after high-fat feeding. Infarct size induced by global ischemia/reperfusion of isolated hearts was similar in both strains at 6 months of age. Aged WT but not KO mice exhibited improved ischemic tolerance compared with the younger group. High-fat feeding for 6 months during aging abolished the infarct size-reduction in WT without affecting KO animals; nevertheless, the extent of injury remained larger in KO mice. The results demonstrate that adverse effects of AMPK α 2-subunit deletion and high-fat feeding on heart function and myocardia l ischemic tolerance in aged female mice are not additive., K. Slámová, F. Papoušek, P. Janovská, J. Kopecký, F. Kolář., and Obsahuje bibliografii
Age-associated changes in large blood vessels were characterized by increased arterial wall thickness, luminal dilation and impaired endothelial function. But little is known about the effect of age on structural and functional changes in small resistance arteries. The mechanisms underlying age-associated endothelial dysfunction in rat mesenteric resistance arteries were investigated in the present study. Small rat mesenteric arteries were excised and cannulated, and vascular endothelial functions were tested by acetylcholine (ACh). Our experiments showed (1) endotheliumdependent vasorelaxation induced by ACh was reduced in aged mesenteric arteries; (2) blockade of Kca channels markedly reduced the vasodilation in young and adult rats, the resultant reduction in aged rats was much smaller compared with young and adult rats; (3) inhibition of endothelial nitric oxide synthase (NOS) resulted in a significant reduction of vasodilation in young and adult, but there was a smaller reduction in aged rats. The results suggest that (1) endothelial function was impaired in mesenteric arteries of aged rats; (2) both Kca channels and nitric oxide (NO) contribute together to the ACh-induced vasorelaxation in small mesenteric arteries, and (3) both the impairment of Kca channel function and decreased NO account for the age-related endothelial dysfunction., E. Zhou, D. Qing, J. Li., and Obsahuje bibliografii a bibliografické odkazy
Considerable evidence demonstrates that phenotypic switching of vascular smooth muscle cells (VSMCs) is influenced by aging and hypertension. During phenotypic switching, VSMCs undergo a switch to a proliferative and migratory phenotype, with this switch being a common pathology in cardiovascular diseases. The aim of this study was to explore the joint influence of age and hypertension on thoracic aortic smooth muscle phenotypic switching and the balance of Akt and mitogen-activated protein kinase (MAPK) signaling during this switch. Different ages of spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) were used to establish hypertension and aging models. The phenotypic state was determined by detecting the marker proteins α-SM-actin, calponin, and osteopontin (OPN) via immunohistochemical staining and Western blot. Signaling proteins associated with the Akt and MAPK pathways were detected in rat thoracic aorta using Western blot. Both aging and hypertension caused a decrease in contractile (differentiated) phenotype markers (α-SM-actin and calponin), while the synthetic (proliferative or de-differentiated) phenotype maker was elevated (OPN). When combining hypertension and aging, this effect was enhanced, with Akt signaling decreased, while MAPK signaling was increased. These results suggested that VSMCs phenotype switching is modulated by a balance between Akt and MAPK signaling in the process of aging and hypertension., Lin Zhang, Zhaoxia Xu, Ying Wu, Jingwen Liao, Fanxing Zeng, Lijun Shi., and Obsahuje bibliografii
The purpose of this study was to determine the effect of a 15-week omega-3 rich diet on age-related differences in myocardial antioxidant defense and inflammation. 20 mature (M) (6 mo.) and 20 old (O) (15 mo.) male Fisher 344 rats were assigned to two diet groups: Control (CON) or Fish Oil (FO). Following the diet, animals were sacrificed and left ventricular (LV) heart tissue was harvested for biochemical assays and western blot analysis. No differences were observed in expression of LV interleukin-6 (IL-6) and tumor necrosis factor-α as well as hydrogen peroxide (H2O2) production between MCON and OCON. However, LV catalase protein expression and activity were increased in OCON vs. MCON and accompanied by increased expression of superoxide dismutase (SOD)-1. In contrast, LV IL-6 was lower in MFO vs. old rats, and LV H2O2 was decreased in MFO and OFO relative to respective control groups. Protein expression and activity of LV catalase and SOD-1 expression were increased in OFO similarly to OCON, but LV SOD activity was also increased in OFO vs. mature rats. In summary, FO supplementation increased myocardial antioxidant defense in all animals and augmented age-associated increases in antioxidant capacity in the absence of changes in inflammation., S. Lennon-Edwards, T. A. Schellhardt, J. M. Kuczmarski., and Obsahuje bibliografii
Baroreflex control of heart rate was studied in inbred salt-sensitive (SS/Jr) and salt-resistant (SR/Jr) Dahl rats that were subjected to chronic dietary sodium chloride loading (for 4 weeks) either in youth or only in adulthood, i.e. from the age of 4 or 12 weeks. Using phenylephrine administration to pentobarbital-anesthetized male rats we have demonstrated the decreased baroreflex sensitivity (lower slope for reflex bradycardia) in young prehypertensive SS/Jr rats fed a low-salt diet as compared to age-matched SR/Jr animals. High salt intake further suppressed baroreflex sensitivity in young SS/Jr but not in SR/Jr rats. Baroreflex sensitivity decreased with age in SR/Jr rats, whereas it increased in SS/Jr rats fed a low-salt diet. Thus at the age of 16 weeks baroreflex sensitivity was much higher in SS/Jr than in SR/Jr animals. High salt intake lowered baroreflex sensitivity even in adult SS/Jr rats without affecting it in adult SR/Jr rats. Nevertheless, baroreflex sensitivity was significantly lower in young SS/Jr rats with a severe salt hypertension than in adult ones with a moderate blood pressure elevation. It is concluded that the alterations of baroreflex sensitivity in young inbred SS/Jr rats (including the response to high salt intake) are similar to those described earlier for outbred salt-sensitive Dahl rats. We have, however, disclosed contrasting age-dependent changes of baroreflex sensitivity in both inbred substrains of Dahl rats., J. Nedvídek, J. Zicha., and Obsahuje bibliografii
The aim of this study was to compare the central and peripheral components of cardiorespiratory fitness during incremental to maximal exercise between older men who were either recreational athletes (RA) or leisurely active (LA) men, i.e., those who fall between trained and untrained. This was a crosssectional study in which all subjects completed an exercise test on a cycle ergometer. Maximal oxygen consumption (VO2max) and ventilatory threshold (VT) were assessed using gas analysis, and central components of VO2max were assessed using a non-invasive thoracic bio-impedance device. VO2max (RA: 45.1±4.8 ml/kg/min; LA: 32.2±4.6 ml/kg/min, p≤0.001) and SV at maximal exercise (RA: 133.5±24.96 ml/beat; LA: 107.9±17.6 ml/beat, p=0.005) were higher in the RA group compared to the LA group. A plateau in SV occurred between 30-45 % of maximal exercise capacity in the RA group. No differences in SV were observed across workloads in the LA group. No differences in the calculated arterio-venous oxygen difference ((a-v)O2diff) were observed between groups. In conclusions, training volume appears to influence central components of cardiorespiratory fitness among a matched sample of older men who are neither trained nor untrained. This builds a case for increasing the volume of training to preserve cardiorespiratory fitness among older men., C. D. O'neill, D. S. Kimmerly, S. Dogra., and Obsahuje bibliografii
The relative length of telomeres measured in peripheral blood leukocytes is a commonly used system marker for biological aging and can also be used as a biomarker of cardiovascular aging. However, to what extent the telomere length in peripheral leukocytes reflects telomere length in different organ tissues is still unclear. Therefore, we have measured relative telomere length (rTL) in twelve different human tissues (peripheral blood leukocytes, liver, kidney, heart, spleen, brain, skin, triceps, tongue mucosa, intercostal skeletal muscle, subcutaneous fat, and abdominal fat) from twelve cadavers (age range of 29 week of gestation to 88 years old). The highest rTL variability was observed in peripheral leukocytes, and the lowest variability was found in brain. We found a significant linear correlation between leukocyte rTL and both intercostal muscle (R=0.68, P<0.02) and liver rTL (R=0.60, P<0.05) only. High rTL variability was observed between different organs from one individual. Furthermore, we have shown that even slight DNA degradation (modeled by sonication of genomic DNA) leads to false rTL shortening. We conclude that the rTL in peripheral leukocytes is not strongly correlated with the rTL in different organs., D. Dlouha, J. Maluskova, I. Kralova Lesna, V. Lanska, J. A. Hubacek., and Obsahuje bibliografii