Accumulating evidence indicates that hypertension is associated with "ion channel remodeling" of vascular smooth muscle cells (VSMCs). The objective of this study was to determine the effects of exercise intensity/volume on hypertension-associated changes in large-conductance Ca2+-activated K+ (BKCa) channels in mesenteric arteries (MAs) from spontaneously hypertensive rats (SHR). Male SHRs were randomly assigned to three groups: a low-intensity aerobic exercise group (SHR-L: 14 m/min), a moderate-intensity aerobic exercise group (SHR-M: 20 m/min), and a sedentary group (SHR). Age-matched Wistar-Kyoto rats (WKYs) were used as normotensive controls. Exercise groups completed an 8-week exercise program. Elevation of the α and β1 proteins was unequal in MA myocytes from SHRs, with the β1 subunit increasing more than the α subunit. BKCa contribution to vascular tone regulation was higher in the myocytes and arteries of SHRs compared to WKYs. SHR BKCa channel subunit protein expression, β1/α ratio, whole cell current density and single-channel open probability was also increased compared with WKYs. Aerobic exercise lowered systemic blood pressure and normalized hypertension-associated BKCa alterations to normotensive control levels in the SHRs. These effects were more pronounced in the moderate-intensity group than in the low-intensity group. There is a dose-effect for aerobic exercise training in the range of low to moderate-intensity and accompanying volume for the correction of the pathological adaptation of BKCa channels in myocytes of MAs from SHR., Y. Zhang, Y. Chen, L. Zhang, N. Lu, L. Shi., and Obsahuje bibliografii
Postconditioning (PostC) is a re cently discovered phenomenon whereby brief repetitive cycles of ischaemia with intermittent reperfusion following prolonged is chaemia elicit cardioprotection. This study investigated whether the age, genetic characteristics or number of repetitive cycles influenced the protective effect of PostC in mice. C57BL/6 floxed or non-floxed STAT-3 mice aged between 14-16 weeks (young) or 18-20 weeks (older) were perfused on a Langendorff apparatus and subjected to 35 min global ischaemia and 45 min reperfusion. PostC was elicited by either 3 (PostC-3) or 6 cycles (PostC-6) of 10s ischaemia and 10 s reperfusion. PostC-3 and PostC-6 in both young and older non-floxed mice reduced the myocar dial infarct size. In contrast, only PostC-3 reduced myocardial infarct size in young floxed mice. Neither PostC-3 nor PostC-6 reduced the in farct in older floxed mice. Our data reveal that genetic characteristics, a minute difference in age or the nu mber of postconditioning cycles are critical factors to be consid ered for the successful effect of ischaemic postconditioning in a murine model. Moreover, these factors should be taken into consideration for future experimental research or clinical applications of this protective phenomenon., S. J. Somers ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
GABA exhibits depolarizing action in the immature neurons due to high intracellular activity of chloride ions. It is maintained by cation-chloride cotransporter NKCC1 which is present in immature brain. Bumetanide is a specific inhibitor of this cotransporter. We studied possible anticonvulsant activity of bumetanide in pentyl enetetrazol-induced seizures in three age groups of rat pups (7, 12, and 18 days old). Pretreatment with bumetanide (0.2-1 mg/kg i.p.) resulted in dose-dependent decrease of incidence of the tonic phase of generalized tonic-clonic seizures in 12-day-old rats only. No effect was observed in younger and older animals. Higher dose of bumetanide (2.5 mg/kg) did not affect tonic convulsions but, on the contrary, decreased latencies of generalized seizures in 12-day-old animals. Lack of marked anticonvulsant effect is probably due to relative maturity of neurons in the brainstem where the generator of generalized seizures is localized. Age- and dose-specific suppression of the tonic phase needs further analysis. and Obsahuje seznam literatury
Altered Ca2+ handling may be responsible for the development of cardiac contractile dysfunctions with advanced age. In the present study, we investigated the roles of oxidative damage to sarcoplasmic reticulum (SR) and expression of Ca2+-ATPase (SERCA 2a) and phospholamban in age-associated dysfunction of cardiac SR. SR vesicles were prepared from hearts of 2-, 6-, 15-, and 26-month-old Wistar rats. Although activity of Ca2+-ATPase decreased with advancing age, no differences in relative amounts of SERCA 2a and phospholamban protein were observed. On the other hand, significant accumulation of protein oxidative damage occurred with aging. The results of this study suggest that agerelated alteration in Ca2+-ATPase activity in the rat heart is not a consequence of decreased protein levels of SERCA 2a and phospholamban, but could arise from oxidative modifications of SR proteins. Cellular oxidative damage caused by reactive oxygen species could contribute to age-related alternations in myocardial relaxation., E. Babušíková ... [et al.]., and Obsahuje seznam literatury
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
The oxidative stress hypothesis of aging suggests that accumulation of oxidative damage is a key factor of the alterations in physiological function during aging. We studied age-related sensitivity to oxidative modifications of proteins and lipids of cardiac sarcoplasmic reticulum (SR) isolated from 6-, 15- and 26-month-old rats. Oxidative stress was generated in vitro by exposing SR vesicles to 0.1 mmol/l FeSO4/EDTA + 1 mmol/l H2O2 at 37 °C for 60 min. In all groups, oxidative stress was associated with decreased membrane surface hydrophobicity, as detected by 1-anilino-8-naphthalenesulfonate as a probe. Structural changes in SR membranes were accompanied by degradation of tryptophan and significant accumulation of protein dityrosines, protein conjugates with lipid peroxidation products, conjugated dienes and thiobarbituric acid reactive substances. The sensitivity to oxidative damage was most pronounced in SR of 26-month-old rat. Our results indicate that aging and oxidative stress are associated with accumulation of oxidatively damaged proteins and lipids and these changes could contribute to cardiovascular injury., E. Babušíková, M. Jeseňák, D. Dobrota, N. Tribulová, P. Kaplán., and Obsahuje bibliografii a bibliografické odkazy
The growth of the prostate gland is androgen-dependent. Testosterone is converted to the most potent dihydrotestosterone (DHT) by 5α-reductase within the prostate. Androgen interacts with androgen receptors (AR) to regulate normal growth of the prostate and has also been implicated in both the progression of benign prostate hyperplasia and prostate cancer. This study was conducted to compare the mRNA expression of AR and 5α-reductase by the prostate gland from three age categories: immature, young-mature and old dogs. Quantitative gene expression was assessed by the real-time PCR and the results were expressed as a relative mRNA expression of the target gene. This study revealed that there was no significant difference in the mRNA expression of the AR gene by the prostate gland of immature, young and old dogs. In contrast, there is a highly significant (P<0.001) down-regulation in 5α-reductase gene by the prostate of young and old dogs as compared with immature dogs. However, there is no significant difference in mRNA expression of the 5α-reductase gene by the prostate gland from young and old dogs. This differential expression of AR and 5α-reductase genes, which are involved in the regulation of androgen effect on prostate gland, might reflect an age-dependent growth requirement of the gland for androgens., F. Shidaifat., and Obsahuje seznam literatury
a1_Fifty years ago, Lewis K. Dahl has presented a new model of salt hypertension – salt-sensitive and salt-resistant Dahl rats. Twenty years later, John P. Rapp has published the first and so far the only comprehensive review on this rat model covering numerous aspects of pathophysiology and genetics of salt hypertension. When we summarized 25 years of our own research on Dahl/Rapp rats, we have realized the need to outline principal abnormalities of this model, to show their interactions at different levels of the organism and to highlight the ontogenetic aspects of salt hypertension development. Our attention was focused on some cellular aspects (cell membrane function, ion transport, cell calcium handling), intra- and extrarenal factors affecting renal function and/or renal injury, local and systemic effects of reninangiotensin-aldosterone system, endothelial and smooth muscle changes responsible for abnormal vascular contraction or relaxation, altered balance between various vasoconstrictor and vasodilator systems in blood pressure maintenance as well as on the central nervous and peripheral mechanisms involved in the regulation of circulatory homeostasis. We also searched for the age-dependent impact of environmental and pharmacological interventions, which modify the development of high blood pressure and/or organ damage, if they influence the saltsensitive organism in particular critical periods of development (developmental windows). Thus, severe self-sustaining salt hypertension in young Dahl rats is characterized by pronounced dysbalance between augmented sympathetic hyperactivity and relative nitric oxide deficiency, attenuated baroreflex as well as by a major increase of residual blood pressure indicating profound remodeling of resistance vessels. Salt hypertension development in young but not in adult Dahl rats can be attenuated by preventive increase of potassium or calcium intake., a2_On the contrary, moderate salt hypertension in adult Dahl rats is attenuated by superoxide scavenging or endothelin-A receptor blockade which do not affect salt hypertension development in young animals., J. Zicha, ... [et al.]., and Obsahuje seznam literatury
The aim of the study was to investigate age-related changes in postural responses to platform translation with 3 various velocities. We focused on the influence of linear velocity using the smoothed profile of platform acceleration (till 100 cm.s−2 ). Eleven healthy young (20-31 years) and eleven healthy elderly (65-76 years) subjects were examined. The subjects stood on the force platform with their eyes closed. Each trial (lasting for 8 sec) with different velocity (10, 15, 20 cm.s−1 ) of 20 cm backward platform translation was repeated 4 times. We have recorded displacements of the centre of pressure (CoP) and the EMG activity of gastrocnemius muscle (GS) and tibialis anterior muscle (TA). The results showed increased maximal values of CoP responses to the platform translation. There was also observed a scaling delay of CoP responses to platform translation with different velocities in elderly. The EMG activity of GS muscle during backward platform translation was of about similar shape in both groups during the slowest platform velocity, but it increased depending on rising velocity. EMG activity of TA was not related to the platform velocity. Early parts of postural responses showed significant co-activation of TA and GS muscles of elderly. It is likely that elderly increased body stiffening in order to help their further balance control., Z. Halická ... [et al.]., and Obsahuje seznam literatury