Nitric oxide (NO) is an important endogenous mediator with significant role in the respiratory system. Many endogenous and exogenous factors influence the synthesis of NO and its level is significantly changed during the inflammation. Analysis of nasal nitric oxide (nNO) is not validated so far as the diagnostic method. There is a lack of reference values with possible identification of factors modulating the nNO levels. In healthy adult volunteers (n=141) we studied nasal NO values by NIOX MINO® (Aerocrine, Sweden) according to the recommendations of the ATS & ERS. Gender, age, height, body weight, waist-to-hip ratio, FEV1/FVC, PEF and numbers of le ukocytes, eosinophils, basophils and monocytes were studied as potential variables influencing the levels of nNO. The complexity of the results allowed us to create a homogenous group for nasal NO monitoring and these data can be used further as the reference data for given variables. Because of significant correlation between nNO and exhaled NO, our results support the "one airway - one disease" concept. Reference values of nasal NO and emphasis of the individual parameters of tested young healthy population may serve as a starting point in the non-invasive monitoring of the upper airway inflammation., M. Antosova, D. Mokra, I. Tonhajzerova, P. Mikolka, P. Kosutova, M. Mestanik, L. Pepucha, J. Plevkova, T. Buday, V. Calkovsky, A. Bencova., and Obsahuje bibliografii
Proximal resistance vessels, such as the mesenteric arteries, contribute substantially to the peripheral resistance. The reactivity of resistance vessels to vasoactive substance like natriuretic peptides plays an important role in the regulation of blood pressure. In current study, we investigated the reactivity of mesenteric arteries to atrial natriuretic peptide (ANP), a well known vasodilating factor, in spontaneously hypertensive rats (SHR), as well as the effects of exercise training on it. As a result, ANP-induced vasorelaxation was attenuated in SHR with significantly increased phosphodiesterase type 5 (PDE5), and decreased cGMP/ANP ratio, compared with WKY rats as control. Intriguingly, the decreased reactivity to ANP in SHR was markedly reversed by exercise training. In addition, ANP resistance of in vitro mesenteric arteries was diminished by sildenafil a potent selective inhibitor of PDE5. In conclusion, ANP resistance occurs in resistance vessels of SHR, suggesting predisposition to hypertension, which can be reversed by exercise., Jun Yu, Bing Zhang, Xing-Lu Su, Ru Tie, Pan Chang, Xue-Ce Zhang, Jian-Bang Wang, Ge Zhao, Miao-Zhang Zhu, Hai-Feng Zhang, Bao-Ying Chen., and Obsahuje bibliografii
The natriuretic peptides - atrial, brain and C-type - were discovered during the last tw enty years. Their effects on cardiovascular, renal, cerebral and other tissues through guanylyl cyclase were uncovered. Over the past decade natriuretic peptides (NPs) became a very useful tool in the management of heart failure patients. Results of many clinical trials have shown that BNP and NT-proBNP are helpful for diagnosis of heart failure. They are also independent markers of prognosis not only in heart failure patients but also in patients with other cardiovascular diseases. Recently published data document the utility of NPs in guiding treatment of heart failure patients. In this article, we focus on basic biochemical and physiological characteristics of NPs as well as on their significance in management of heart failure patients. Some limitations and pitfalls of NPs levels interpretation in diagnosing heart failure are also discussed., J. Krupička ... [et al.]., and Obsahuje seznam literatury
Renal medullary endothelin B receptors (ETB) mediate sodium excretion and blood pressure (BP) control. Several animal models of hypertension have impaired renal medullary ETB function. We found that 4-week high-caloric diet elevated systolic BP in Dahl salt-sensitive (Dahl S) rats (126±2 vs. 143±3 mm Hg, p<0.05). We hypothesized that renal medullary ETB function is dysfunctional in DS rats fed a high-caloric diet. We compared the diuretic and natriuretic response to intramedullary infusion of ETB agonist sarafotoxin 6c (S6c) in DS rats fed either a normal or high-caloric diet for 4 weeks. Urine was collected during intramedullary infusion of saline for baseline collection followed by intramedullary infusion of either saline or S6c. We first examined the ETB function in DS rats fed a normal diet. S6c increased urine flow (2.7±0.3 μl/min during baseline vs. 5.1±0.6 μl/min after S6c; p<0.05; n=5) and sodium excretion (0.28±0.05 vs. 0.81±0.17 μmol/min; p<0.05), suggesting that DS rats have renal medullary ETB function. However, DS rats fed a high-caloric diet displayed a significant increase in urine flow (2.7±0.4 vs. 4.2±0.4 μl/min, baseline vs. S6c infusion, respectively; p<0.05, n=6), but no significant change in sodium excretion in response to S6c (0.32±0.06 vs. 0.45±0.10 μmol/min). These data demonstrate that renal medullary ETB function is impaired in DS rats fed a high-caloric diet, which may be contributed to the elevation of blood pressure during high-caloric feeding in this model., W. Kittikulsuth, K. A. Hyndman, J. S. Pollock, D. M. Pollock., and Seznam literatury
Cardiovascular disease, while rare in women of reproductive age, is the main cause of mortality in menopause. The purpose of our study was to determine the association of natural menopause with cardiovascular risk factors, including their clustering into metabolic syndrome (MS). A random 5 % representative population sample of women aged 45-54 years was examined. In 575 women, we were able to determine their natural reproductive aging status. Multiple regression analysis was used to calculate the association between age, menopausal status, and risk factors under study. After adjustment for age, there was an increase in the odds ratio of developing MS, as defined by NCEP (OR=2.0; 95 % CI [1.1; 3.7]), and an increase in plasma lipid ratios (total cholesterol/HDL-C, LDL-C/HDL-C, apolipoprotein-B/ apolipoprotein-A1; p<0.05 for all) in postmenopausal women. Age, but not menopausal status, was associated with some single components of MS; only waist circumference significantly increased after menopause, independently of age. Clustering of risk factors in MS and lipid ratios (combined factors) was strongly associated with menopause whereas worsening of single components of MS was strongly associated with age. In conclusion, based on our results, the menopause may pose a risk to women through clustering of cardiovascular risk factors beyond simple aging., M. Lejsková ... [et al.]., and Obsahuje seznam literatury
Recently, the genetic cause of several syndromic forms of glycemia dysregulation has been described. One of them, MEHMO syndrome, is a rare X-linked syndrome recently linked to the EIF2S3 gene mutations. MEHMO is characterized by Mental retardation, Epilepsy, Hypogonadism/hypogenitalism, Microcephaly, and Obesity. Moreover, patients with MEHMO had also diabetes and endocrine phenotype, but detailed information is missing. We aimed to provide more details on the endocrine phenotype in two previously reported male probands with MEHMO carrying a frame-shift mutation (I465fs) in the EIF2S3 gene. Both probands had a neonatal hypoglycemia, early onset insulindependent diabetes, and hypopituitarism due to dysregulation and gradual decline of peptide hormone secretion. Based on the clinical course in our two probands and also in previously published patients, neonatal hypoglycemia followed by earlyonset diabetes and hypopituitarism may be a consistent part of the MEHMO phenotype., J. Staník, M. Škopková, D. Staníková, K. Brennerová, L. Barák, L. Tichá, J. Hornová, I. Klimeš, D. Gasperiková., and Seznam literatury
To test the hypothesis that neonatal GLP-1 exposure may program myosin heavy chain (MyHC) composition in adult skeletal muscle, two-day-old rats were transfected intramuscularly with vacant vector plasmid (VP), or recombinant plasmid expressing secretory GLP-1 at the doses of 60 μg (LG) and 120 μg (HG), respectively. Expression of GLP-1 mRNA was detected in muscles of both LG and HG rats 7 days after transfection, with more abundant GLP-1 transcript seen in LG rats. In accordance with the GLP-1 expression, LG rats demonstrated more significant responses to neonatal GLP-1 exposure. Small yet significant growth retardation was observed in LG rats, which is accompanied with significantly reduced serum insulin concentration at 8 weeks of age compared to VP rats. The responses of skeletal muscle were dependent on muscle type. Significant increase of PGC-1α and GLUT4 mRNA expression was detected in soleus of LG rats, whereas a MyHC type switch from ⅡB to Ⅰ was seen in gastrocnemius. These results indicate that neonatal exposure of healthy pups to ectopic GLP-1 causes growth retardation with decreased serum insulin as well as muscle type-dependent modifications in MyHC type composition and metabolic gene expression in adult rats., L. Wang ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Although there are abundant data on ischemic postconditioning (IPoC) in the adult myocardium, this phenomenon has not yet been investigated in neonatal hearts. To examine possible protective effects of IPoC, rat hearts isolated on days 1, 4, 7 and 10 of po stnatal life were perfused according to Langendorff. Developed force (DF) of contraction was measured by an isometric force transducer. Hearts were exposed to 40 or 60 min of global ischemia followed by reperfusion up to the maximum recovery of DF. IPoC wa s induced by three cycles of 10, 30 or 60 s periods of global ischemia/reperfusion. To further determine the extent of ischemic injury, lactate dehydrogenase (LDH) release was measured in the coronary effluent. Tolerance to ischemia did not change from day 1 to day 4 but decreased to days 7 and 10. None of the postconditioning protocols tested led to significant protection on the day 10. Prolonging the period of sustained ischemia to 60 min on day 10 did not lead to better protection. The 3x30 s protocol wa s then evaluated on days 1, 4 and 7 without any significant effects. There were no significant differences in LDH release between postconditioned and control groups. It can be concluded that neonatal hearts cannot be protected by ischemic postconditioning during first 10 days of postnatal life. and J. Doul, Z. Charvátová, I. Ošťádalová, M. Kohutiar, H. Maxová, B. Ošťádal.
The endothelin (ET) and prorenin/renin/prorenin receptor (PRR) systems have opposing physiological effects on collecting duct (CD) salt and water reabsorption. It is unknown if the CD ET and renin/PRR systems interact, hence we examined the effects of deleting CD renin or nephron PRR on CD ET system components. PRR knockout (KO) mice were polyuric and had markedly increased urinary ET-1 and inner medullary CD (IMCD) ET-1 mRNA. PRR KO mice had greatly increased IMCD ETA receptor mRNA and protein, while ETB mRNA and protein were decreased. Water loaded wild-type mice with similar polyuria as PRR KO mice had modestly increased urinary ET-1 excretion and inner medullary ET-1 mRNA, while inner medullary ETA and ETB mRNA or protein expression were unaffected. In contrast to PRR KO, CD prorenin/renin KO did not alter ET system components. Taken together, these results suggest that the nephron PRR is involved in regulating CD ET system expression, but this effect may be independent of CD-derived renin., N. Ramkumar, D. Stuart, N. Abraham, D. E. Kohan., and Seznam literatury
We used a model of tibial lengthening in rabbits to study the postoperative pain pattern during limb-lengthening and morphological changes in the dorsal root ganglia (DRG), including alteration of substance P (SP) expression. Four groups of animals (naïve; OG: osteotomized only group; SDG/FDG: slow/fast distraction groups, with 1 mm/3 mm lengthening a day, respectively) were used. Signs of increasing postoperative pain were detected until the 10th postoperative day in OG/SDG/FDG, then they decreased in OG but remained higher in SDG/FDG until the distraction finished, suggesting that the pain response is based mainly on surgical trauma until the 10th day, while the lengthening extended its duration and increased its intensity. The only morphological change observed in the DRGs was the presence of large vacuoles in some large neurons of OG/SDG/FDG. Cell size analysis of the S1 DRGs showed no cell loss in any of the three groups; a significant increase in the number of SP-positive large DRG cells in the OG; and a significant decrease in the number of SP-immunoreactive small DRG neurons in the SDG/FDG. Faster and larger distraction resulted in more severe signs of pain sensation, and further reduced the number of SP-positive small cells, compared to slow distraction., K. Pap, Á. Berta, G. Szöke, M. Dunay, T. Németh, K. Hornok, L. Marosföi, M. Réthelyi, M. Kozsurek, Z. Puskár., and Obsahuje bibliografii