Akt kinase regulates numerous cell functions including glucose metabolism, cell growth, survival, protein synthesis, and control of local hemodynamics. mTOR is one of down-stream effectors of Akt involved in the initiation of protein translation. However, renal Akt signaling in Type 1 diabetes (DM) in vivo, in particular under the conditions reflecting differences in metabolic control, has received less attention. Renal cortical activity and expression of Akt and mTOR (kinase assay, western blotting) were determined in streptozotocin-diabetic rats (D) with different levels of glycemic control (blood glucose 22.0± 1.0, 13.4±1.5, 8.1±0.4 mmol/l, p<0.05 between the groups), achieved by varying insulin treatment (0,4 and 12 IU/day), and in control rats with (C4) or without (C) chronic insulin administration. Renal Akt activity was reduced in D rats without insulin treatment and severe hyperglycemia (D-0, -62 %, p<0.01 vs. C), partially restored in moderately hypergly cemic rats (D-4, -30 %, p<0.05 vs. C), and normalized in D rats with intensive insulin and tight metabolic control (D-12). Expression of active mTOR paralleled Akt activity in D-0 (-51 %, p<0.01 vs. C), but not in D-4 and D- 12 that demonstrated increases in active mTOR (+55 %, +80 % resp., p<0.05) as compared to C. Moreover, insulin activated renal Akt (+82 %, p<0.01), but not mTOR in C4. In conclusion, glycemic control and intensity of insulin treatment are important modulators of renal Akt and mTOR activity in diabetes. While Akt activity is reversible by tight metabolic control, combination of hyperglycemia and insulin treatment resulted in enhancement of mTOR activity. In addition to Akt, other signaling pathways likely contribute to regulation of renal mTOR activity in diabetes., J. Ždychová, J. Veselá, L. Kazdová, R. Komers., and Obsahuje bibliografii a bibliografické odkazy
Previous investigations revealed that most of the fluid regulating hormones showed no consistent relationship to the hypoxic diuretic response (HDR). In this study we examined if adrenomedullin (AM), a hypoxia-mediated diuretic/natriuretic peptide is connected to HDR. Thirty-three persons were examined at low altitude (LA), on the third exposure day at 3440 m (medium altitude, MA) and on the fourteenth day at 5050 m (high altitude, HA). Nocturnal diuresis rose from 460 ml [interquartile range 302 ml] at LA to 560 [660] ml at MA to 1015 [750] ml at HA (p<0.005). Sodium excretion was similar at LA and MA (41.8 [27.0] vs. 41.4 [28.4] mM) and increased to 80.2 [29.1] mM at HA (p<0.005). Urinary AM excretion was 7.9 [3.9] at LA, 7.5 [5.7] pM at MA, and increased to 10.5 [5.1] pM (p<0.05) at HA. Urinary AM excretion was correlated to diuresis (r=0.72, p<0.005) and sodium excretion (r=0.57, p<0.005). Plasma AM concentration rose from 16.4 [3.1] to 18.8 [4.9] pM/l at MA (p<0.005) and to 18.3 [4.3] pM/l at HA (p<0.005). Plasma AM concentration and urinary AM excretion were not correlated, neither were plasma AM concentration and diuresis or natriuresis. Our data suggest the involvement of increased renal AM production in the pathophysiology of high altitude fluid and sodium loss., B. Haditsch, A. Roessler, H. G. Hinghofer-Szalkay., and Obsahuje bibliografii a bibliografické odkazy
The relationship between obesity and renal lesions, especially in low estrogen levels, has been less documented. The aim of this study was to assess the renal changes in diet-induced obesity in ovariectomized rats. Wistar rats were ovariectomized or shamoperated and divided into four groups: sham-operated rats fed a standard diet (SSD); ovariectomized rats fed a standard diet (OSD); sham-operated rats fed a high-fat diet (SHFD); ovariectomized rats fed a high-fat diet (OHFD). Body weight and blood pressure were measured weekly. The rats were killed 24 weeks after initiation of standard or high-fat diet treatment, the kidneys were removed for immunohistochemical and histological studies. Blood and urine samples were collected to quantify sodium, potassium and creatinine. OHFD rats presented increases in visceral adipose tissue, serum insulin levels, blood pressure and proteinuria, and a decrease in fractional excretion of sodium as well. Histological and morphometric studies showed focal alterations in the renal cortex. Expression of macrophages, lymphocytes, nuclear factor-kappa B (NF-B), Proliferating Cell Nuclear Antigen (PCNA), angiotensin II (ANG II) and vimentin was greater in OHFD rats than in control rats. Thus, these results demonstrate that the high-fat diet in ovariectomized rats promoted renal function and structure changes, renal interstitial infiltration of mononuclear cells and increased expression of ANG II and NF-κB., L. S: B. Amaral, J. A. Silva, T. M. Trindade, W. B. D. Ribas, C. L. Macedo, T. M. Coimbra, N. O. Belo, A. C. M. Magalhães, T. J. Soares., and Obsahuje bibliografii
The influence of renal nerves on the effects of concurrent NO synthase inhibition (10 mg kg-1 b.w. i.v. L-NAME) and ETA/ETB receptor inhibition (10 mg kg-1 b.w. i.v. bosentan) on renal excretory function and blood pressure in conscious spontaneously hypertensive rats (SHR) was investigated. L-NAME increased blood pressure, urine flow rate, fractional excretion of sodium, chloride and phosphate in both normotensive Wistar rats and SHR with intact renal nerves (p<0.01). GFR or RBF did not change in any of the groups investigated. The effects of L-NAME on renal excretory function were markedly reduced by bosentan and the values returned to control level in the normotensive rats, while in SHR the values were reduced by bosentan, but they remained significantly elevated as compared to control level (p<0.05). The hypertensive response induced by L-NAME in SHR is partially due to activation of endogenous endothelins, but it does not depend on renal nerves. Chronic bilateral renal denervation abolished the effect of L-NAME on sodium and chloride excretion in normotensive rats, whereas it did not alter this effect in SHR. The participation of endogenous endothelins in changes of renal excretory function following NO synthase inhibition is diminished in SHR as compared to Wistar rats., R. Girchev, P. Markova., and Obsahuje bibliografii a bibliografické odkazy
Varied causative and risk factors can lead to cardiac dysfunction. Cardiac dysfunction often evolves into heart failure by cardiac remodeling due to autonomic nervous system disturbance and neurohumoral abnormalities, even if the detriment factors are removed. Renal sympathetic nerve activity plays a pivotal regulatory role in neurohumoral mechanisms. The present study was designed to determine the therapeutic eff ects of renal sympathetic denervation (RSD) on cardiac dysfunction, fibrosis, and neurohumoral response in transverse aortic constriction (TAC) rats with chronic pressure overload. The present study demonstrated that RSD attenuated myocardial fibrosis and hypertrophy, and structural remodeling of the left atrium and ventricle, up -regulated cardiac β adrenoceptor (β -AR, including β 1 AR and β 2 AR) and sarco -endoplasmic reticulum Ca 2+ -ATP ase (SERCA) while down -regulated angiotensin II type 1 receptor (AT 1 R), and decreased plasma B -type natriuretic peptide (BNP), norepinephrine (NE) , angiotensin II (Ang II), and arginine vasopressin (AVP) levels in TAC rats with chronic pressure overload. We conclude that RSD attenuates myocardial fibrosis, the left atrial enlargement, and the left ventricular wall hypertrophy; inhibits the overdrive of the sympathetic ner vous system (SNS), renin- angiotensin -aldosterone system (RAAS), and AVP system in TAC rats with chronic pressure overload . RSD could be a promising non -pharmacological approach to control the progression of cardiac dysfunction., Z.-Z. Li, H. Jiang, D. Chen, Q. Liu, J. Geng, J.-Q. Guo, R.-H. Sun, G.-Q. Zhu, Q.-J. Shan., and Obsahuje bibliografii
Chronic kidney disease (CKD) is a life-threatening disease arising as a frequent complication of diabetes, obesity and hypertension. Since it is typically undetected for long periods, it often progresses to end-stage renal disease. CKD is characterized by the development of progressive glomerulosclerosis, interstitial fibrosis and tubular atrophy along with a decreased glomerular filtration rate. This is associated with podocyte injury and a progressive rise in proteinuria. As endothelin-1 (ET-1) through the activation of endothelin receptor type A (ETA) promotes renal cell injury, inflammation, and fibrosis which finally lead to proteinuria, it is not surprising that ETA receptors antagonists have been proven to have beneficial renoprotective effects in both experimental and clinical studies in diabetic and non-diabetic CKD. Unfortunately, fluid retention encountered in large clinical trials in diabetic CKD led to the termination of these studies. Therefore, several advances, including the synthesis of new antagonists with enhanced pharmacological activity, the use of lower doses of ET antagonists, the addition of diuretics, plus simply searching for distinct pathological states to be treated, are promising targets for future experimental studies. In support of these approaches, our group demonstrated in adult subtotally nephrectomized Ren-2 transgenic rats that the addition of a diuretic on top of renin-angiotensin and ETA blockade led to a further decrease of proteinuria. This effect was independent of blood pressure which was normalized in all treated groups. Recent data in non-diabetic CKD, therefore, indicate a new potential for ETA antagonists, at least under certain pathological conditions., I. Vaněčková, S. Hojná, M. Kadlecová, Z. Vernerová, L. Kopkan, L. Červenka, J. Zicha., and Seznam literatury
Disturbed circadian activity of the sympathetic system may be involved in negative consequences of chronodisruption on the cardiovascular system. We studied daily changes in pressure response to adrenergic stimulation in rats exposed to repeated phase advance shifts (PAS) of light/dark (LD) regimen. Blood pressure (BP), heart rate (HR) and locomotor activity was measured by radiotelemetry in normotensive Wistar rats exposed to repeated PAS (three 8-h shifts per week) lasting for 12 weeks. Norepinephrine was administered subcutaneously in the middle of L and D during week 12 of PAS exposure. In the control LD cycle, cardiovascular parameters exhibited significant daily rhythms with expected higher values during D than L phase. Rats exposed to PAS showed disturbed rhythms without a BP and HR increase. Administration of norepinephrine to control rats revealed daily variability in the cardiovascular response with higher stimulation of BP during L than D. This daily pattern of BP response to norepinephrine was diminished in the PAS group. The damped daily variability in pressure response to norepinephrine and augmented response during the light phase of the day suggest that the increased and desynchronized activity of the sympathetic system may worsen responses of the cardiovascular system to load in individuals exposed to irregular LD conditions., L. Molcan, A. Vesela, M. Zeman., and Obsahuje bibliografii
T wave morphology (TWM) descriptors derived from Holter electrocardiograms during hemodialysis (HD) are of potential value for cardiac risk assessment in HD patients. Our knowledge on autonomic regulation of TWM descriptors is limited. The purpose of this study was to investigate the association between TWM parameters and heart rate variability (HRV) during intradialytic monitoring. In each of 81 patients on maintenance HD, continuous electrocardiograms were recorded 5 times during HD on alternate weeks. TWM descriptors were calculated every 5 s in overlapping 10-s ECG segments and Low Frequency (LF) (0.04 Hz to 0.15 Hz), High Frequency (HF) (0.15 Hz to 0.40 Hz) powers of the spectrum of HRV were calculated every five min. The calculated values of TWM and HRV were averaged during the first hour of the recordings and subsequently over all recordings in each subject. Analyzable data for HRV and TWM were available in 71 HD patients (aged 61±15, 36 % diabetics, 32 % females). LF in normalized units correlated positively with Total Cosine R to T (r=0.374, p=0.001) and negatively with T wave morphology dispersion (r=-0.253, p=0.033) after adjusting for heart rate. A heart rate independent association between repolarisation descriptors and HRV exists in HD patients. Autonomic modulation needs to be considered when using TWM characteristics for risk profiling of HD patients., D. Poulikakos, D. Banerjee, M. Malik., and Obsahuje bibliografii
The cardiovascular system is described by parameters including blood flow, blood distribution, blood pressure, heart rate and pulse wave velocity. Dynamic changes and mutual interactions of these parameters are important for understanding the physiological mechanisms in the cardiovascular system. The main objective of this study is to introduce a new technique based on parallel continuous bioimpedance measurements on different parts of the body along with continuous blood pressure, ECG and heart sound measurement during deep and spontaneous breathing to describe interactions of cardiovascular parameters. Our analysis of 30 healthy young adults shows surprisingly strong deep-breathing linkage of blood distribution in the legs, arms, neck and thorax. We also show that pulse wave velocity is affected by deep breathing differently in the abdominal aorta and extremities. Spontaneous breathing does not induce significant changes in cardiovascular parameters., P. Langer, P. Jurák, V. Vondra, J. Halámek, M. Mešťaník, I. Tonhajzerová, I. Viščor, L. Soukup, M. Matejkova, E. Závodná, P. Leinveber., and Obsahuje bibliografii
Determination of response of cortisol and its metabolites to different stimuli may be important for adrenal gland disorders. To date, only one metabolite, cortisone, has been followed in stimulation tests of the adrenal gland. We aimed to describe a response of cortisol metabolites to the standard short Synacthen test (HDST), insulin tolerance test (ITT), low dose Synacthen test (LDST) and medium dose Synacthen test (MDST). Sixty healthy subjects were investigated: 30 men and 30 women. Plasma for measurements of cortisol and its metabolites was obtained before and 30th and 60th min after Synacthen and insulin administration. The cut-off 500 nmol/l of cortisol was reached after stimulation in all of tests, the maximal stimulation level was reached in 60th min in all of the tests except for LDST. The response of cortisol and its metabolites at 30th and 60th min strongly correlated in all of the tests except for LDST. Cortisol and its metabolites increased after stimulation; in contrast, cortisone and its metabolites decreased. We showed that the response of the cortisol metabolites during the Synacthen tests and ITT well correlated, and the MDST showed similar response compared to HDST. The decrease in cortisone metabolites may correspond to the regeneration of cortisol from cortisone in response to stimulation test., K. Simunkova, M. Duskova, M. Kosak, M. Krsek, V. Hana, M. Hill, H. Jandikova, H. Pospisilova, M. Sramkova, E. Bifulco, L. Starka., and Obsahuje bibliografii