Search

Aim: The intraglomerular mesangial cells are located between the glomerular capillaries. Here we hypothesized that mesangial cells regulate the single nephron glomerular filtration rate (snGFR) and that mesangial cells support the integrity of the glomerular filtration barrier. Methods: We assessed the function of mesangial cells in vivo by multiphoton microscopy. Mesangial cells were depleted in Munich Wistar Froemter rats using the Thy1.1 antibody model. Results: The Thy1.1 antibody caused the cell‐specific loss of 82 ± 3% of mesangial cells. After mesangial cell depletion, the baseline snGFR was reduced to 12.0 ± 1.2 vs 32.4 ± 3.2 nL/min in controls. In control rats, the snGFR decreased after angiotensin II infusion by 61 ± 3% (P =.004), whereas it remained unchanged in Thy1.1‐treated rats. The changes in the snGFR after angiotensin II infusion in control rats were accompanied by the marked rotation of the capillary loops within Bowman's space. This phenomenon was absent in anti‐Thy1.1‐treated rats. The glomerular sieving coefficient (GSCA) for albumin, used as a measure of the integrity of the glomerular filtration barrier, was low in control rats (0.00061 ± 0.00004) and increased after angiotensin II infusion (0.00121 ± 0.00015). In Thy1.1‐treated rats, the GSC was elevated (0.0032 ± 0.00059) and did not change in response to angiotensin II. Electron microscopy revealed the increased thickness of the glomerular basement membrane after mesangial cell depletion. Conclusion: Our data suggest that mesangial cells actively contribute to the regulation of the snGFR. Furthermore, mesangial cells are crucially involved in maintaining the integrity of the glomerular filtration barrier, in part by modulating the thickness of the glomerular basement membrane. [ABSTRACT FROM AUTHOR]

Abstract: Aim: Here, we have extensively investigated the relationship between thermoregulation and neurodegeneration‐induced dementia of the Alzheimer's type using intracerebroventricular injections of streptozotocin (icv‐STZ). Methods: Male Wistar rats were treated with bilateral injections of icv‐STZ, and their thermoregulatory profiles (core body temperature, tail‐skin temperature, cold and heat defence responses and thermal place preference) were evaluated. Spatial memory, locomotor activity, social interaction, brain ventricular volume, and Aβ1‐42 and tau protein levels in the brain were analysed to characterize the effects of STZ on the brain and behaviour. Results: In addition to deficits in spatial memory, reduced social interaction and an increased brain ventricular volume, icv‐STZ rats presented a pattern of hyperthermia, as demonstrated by an increased core body temperature. Hyperthermia was due to the activation of both autonomic heat conservation and behavioural cold avoidance, as STZ‐treated rats presented tail‐cutaneous vasoconstriction and an altered thermal preference. They also showed a distinct cold defence response when exposed to cold. Conclusion: Our data bring evidence that icv‐STZ in rats causes hyperthermia, with activation of both autonomic and behavioural thermoregulatory defence responses when challenged at colder temperatures, leading us to hypothesize that they are more efficient in preventing hypothermia. These data are relevant for a better understanding of neurodegenerative disease mechanisms. [ABSTRACT FROM AUTHOR]

The article discusses possible effective antiarrhythmic therapies for chronic atrial fibrillation (AF), particularly the novel pharmacological agents and principles that were studied by the Elinder group. Also cited are the use of mouse atrial myocyte in culture and selected natural compounds (resin acids) in the study, and the effectiveness of the acids in altering the activity of several different transmembrane ionic currents responsible for creating atrial action.

Aim The Na+/H+ exchanger NHE3 activity decreases in the proximal tubule of spontaneously hypertensive rats ( SHRs) as blood pressure increases, and this reduction is correlated with higher NHE3 phosphorylation levels at the PKA consensus site serine 552. This study tested the hypothesis that this lowered NHE3 activity is associated with an increase in PKA activity and expression, and/or a decrease in protein phosphatase-1 ( PP1) activity and expression. Methods Proximal tubule NHE3 activity was measured as the rate of bicarbonate reabsorption by stationary microperfusion. NHE3 phosphorylation and protein expression were determined by immunoblotting. PKA and PP1 activities were determined using specific substrates under optimal enzymatic conditions. Results The PKA activator, 6-MB- cAMP, increased the phosphorylation levels of NHE3 at serine 552 in the renal cortex; this increase happens to a much greater extent in young pre-hypertensive SHRs (Y-SHRs) compared to adult SHRs with established hypertension (A-SHRs). Likewise, the inhibitory effect of 6-MB- cAMP on NHE3 transport activity was much more pronounced in the proximal tubules of Y-SHRs than in those of A-SHRs. Renal cortical activity of PKA was not significantly different between Y-SHRs and A-SHRs. On the other hand, Y-SHRs exhibited higher protein phosphatase 1 (PP1) activity, and their expression of the PP1 catalytic subunit PP1 α in the renal cortex was also higher than in A-SHRs. Conclusion Collectively, these results support the idea that the lower NHE3 transport activity and higher phosphorylation occurring after the development of hypertension in SHRs are due, at least in part, to reduced PP1-mediated dephosphorylation of NHE3 at serine 552. [ABSTRACT FROM AUTHOR]

Aim Rats selectively bred for inborn low capacity of running ( LCR) display a series of poor health indices, whereas rats selected for high capacity of running ( HCR) display a healthy profile. We hypothesized that selection of low aerobic capacity over generations leads to a phenotype with increased diastolic Ca2+ leak that trigger arrhythmia. Methods We used rats selected for HCR ( N = 10) or LCR ( N = 10) to determine the effect of inborn aerobic capacity on Ca2+ leak and susceptibility of ventricular arrhythmia. We studied isolated Fura-2/ AM-loaded cardiomyocytes to detect Ca2+ handling and function on an inverted epifluorescence microscope. To determine arrhythmogenicity, we did a final experiment with electrical burst pacing in Langendorff-perfused hearts. Results Ca2+ handling was impaired by reduced Ca2+ amplitude, prolonged time to 50% Ca2+ decay and reduced sarcoplasmic reticulum ( SR) Ca2+ content. Impaired Ca2+ removal was influenced by reduced SR Ca2+ ATP-ase 2a ( SERCA2a) function and increased sodium/Ca2+ exchanger ( NCX) in LCR rats. Diastolic Ca2 leak was 87% higher in LCR rats. The leak was reduced by Ca MKII inhibition. Expression levels of phosphorylated threonine 286 Ca MKII levels and increased RyR2 phosphorylation at the serine 2814 site mechanistically support our findings of increased leak in LCR. LCR rats had significantly higher incidence of ventricular fibrillation. Conclusion Selection of inborn low aerobic capacity over generations leads to a phenotype with increased risk of ventricular fibrillation. Increased phosphorylation of Ca MKII at serine 2814 at the cardiac ryanodine receptor appears as an important mechanism of impaired Ca2+ handling and diastolic Ca2+ leak that results in increased susceptibility to ventricular fibrillation. [ABSTRACT FROM AUTHOR]

Aim To examine whether sympathetic afferent stimulation ( SAS) inhibits central vagal activation induced by α2-adrenergic stimulation. Methods In anaesthetized Wistar-Kyoto rats, a cardiac microdialysis technique was applied to the left ventricle, and the effect of α2-adrenergic stimulation by medetomidine on myocardial interstitial acetylcholine ( ACh) levels was examined in the absence ( n = 6) or the presence ( n = 6) of SAS delivered from the left stellate ganglion. The effect of electrical vagal efferent stimulation on myocardial interstitial ACh release was also examined in the absence or the presence of SAS ( n = 6). Results Intravenous medetomidine (0.1 mg kg−1) significantly increased myocardial interstitial ACh levels in the absence of SAS (from 1.95 ± 0.79 to 3.36 ± 1.61 n m, P < 0.05), but not in the presence of SAS (from 1.67 ± 0.67 to 2.01 ± 0.78 n m). In contrast, electrical vagal nerve stimulation increased myocardial interstitial ACh level to the same degree regardless of SAS (from 1.66 ± 0.16 to 3.93 ± 0.72 n m without SAS vs. 4.05 ± 0.89 n m with SAS). Conclusion Sympathetic afferent stimulation inhibited medetomidine-induced ACh release, but not electrical stimulation-induced ACh release, suggesting that SAS inhibited medetomidine-induced vagal activation via central mechanisms. While central vagal activation by α2-adrenergic agonists could be an alternative to electrical vagal activation, blocking sympathetic afferent input may be important to increase the efficacy of α2-adrenergic agonists in enhancing vagal nerve activity. [ABSTRACT FROM AUTHOR]

Aim Gamma-aminobutyric acid ( GABA)-ergic transmission from the hypothalamus is essential for normal feeding regulation, and hyperphagia can be induced by local application of GABAA-receptor agonists to different feeding-associated brain areas. The food intake in rats varies diurnally and that may influence the effect of GABAA-receptor active compounds. The progesterone metabolite allopregnanolone is a highly potent endogenous positive modulator of the GABAA receptor. Therefore, it is easy to envisage that allopregnanolone would have a hyperphagic effect, but earlier reports in rat have given ambiguous results. However, a contributing factor for the discrepancy may be the time point of the diurnal cycle in which the experiments were performed. The aim of this study was to investigate the effect of allopregnanolone on intake of standard chow in male Wistar rats at different time points of the day. Methods Chow intake was measured after acute administration of allopregnanolone, and feeding behaviour was analysed to detect meal patterns. Results We found that allopregnanolone increased chow intake by up to four times in the dark part of the 24-h cycle. The rats ate significantly more, and the effect of allopregnanolone was more prominent in the active (dark) compared with the inactive (light) period. Allopregnanolone also reduced feeding latency and prolonged the meal duration compared with vehicle. Conclusion Allopregnanolone seems to act at several levels of feeding regulation, that is, to initiate feeding and to prolong the duration of a meal, thereby increasing the meal size, especially in the dark period of the 24-h cycle. [ABSTRACT FROM AUTHOR]

Aim Protein kinases, activated by vasodilator substances, affect vascular function by regulating large conductance Ca2+-activated K+ ( KCa1.1) channels. Thus, the aim of the present investigation was to address the hypothesis that quercetin-induced vasorelaxation is caused by a PKG-mediated stimulation of KCa1.1 currents. Methods Single freshly isolated myocytes and endothelium-denuded rings of the rat tail main artery were employed for electrophysiological and contractility measurements respectively. Results Quercetin relaxed vessels and increased KCa1.1 currents in a concentration-dependent manner: both effects were antagonized by the specific KCa1.1 channel blocker iberiotoxin. Stimulation of KCa1.1 currents was fully reversible upon drug washout, markedly reduced by Rp-8-Br- PET- cGMPs, a PKG-inhibitor, but not affected by catalase. Quercetin shifted by 34.3 mV the voltage dependence of KCa1.1 channel activation towards more negative membrane potentials without affecting its slope. Under conditions of tight functional coupling between sarcoplasmic reticulum Ca2+ release sites and KCa1.1 channels, quercetin decreased both the frequency and the amplitude of KCa1.1 transient currents in a ryanodine-like manner. Conclusion The natural flavonoid quercetin relaxes the rat tail main artery partly via a PKG-mediated stimulation of smooth muscle KCa1.1 channels. [ABSTRACT FROM AUTHOR]

Aim Mechanisms underlying cardiac contractile dysfunction during and after rewarming from hypothermia remain largely unknown. We have previously reported myocardial post-hypothermic calcium overload to be the culprit. The aim of the present study was to measure changes in myocardial [ Ca2+]i during graded hypothermia and after rewarming in an anesthetized, intact rat model, using the 45 Ca2+ technique. Methods Rats were randomized and cooled to 15 ° C. Hearts were excised and perfusion-washed to remove extracellular calcium after 0.5 h of hypothermia ( n = 9), 4 h of hypothermia ( n = 8), and after 4 h of hypothermia and 2 h rewarming ( n = 9). A normothermic group, kept at 37 ° C for 5 h, served as control ( n = 6). [ Ca2+]i was determined in perchloric acid extracts of heart tissue. Spontaneous cardiac electromechanic work was maintained during hypothermia without cardiac arrest or ischaemia. Results Between 0.5 and 4 h at 15 ° C, a six-fold increase in cardiac [ Ca2+]i was observed (0.55 ± 0.10 vs. 2.93 ± 0.76 μmol (g dry wt)−1). Rewarming resulted in a 33% decline in [ Ca2+]i, but the actual value was significantly above the value measured in control hearts. Conclusion We show that calcium overload is a characteristic feature of the beating heart during deep hypothermia, which aggravates by increasing duration of exposure. The relatively low decline in [ Ca2+]i during the rewarming period indicates difficulties in recovering calcium homoeostasis, which in turn may explain cardiac contractile dysfunction observed after rewarming. [ABSTRACT FROM AUTHOR]

Aim In this study, we investigated the regulatory network of the key and rate-limiting enzyme of cholesterol biosynthetic pathway, the 3-hydroxy 3-methylglutaryl coenzyme A reductase ( HMGR) in different brain regions, to add new insight about lipid metabolism and physiology in the central nervous system ( CNS). Methods HMGR levels and activation state and the proteins involved in the enzyme regulatory network were analysed by Western blot in hippocampus, cortex, cerebellum and brain stem of adult male rats. Results HMGR protein level and phosphorylation state exhibit a specific pattern in each brain area analysed, according to the levels and activation state of the proteins responsible for the short- and long-term regulation of the enzyme. Moreover, low-density lipoprotein receptor expression displays a similar trend to that of HMGR. Conclusions The obtained data indicate that cholesterol biosynthesis could be differently modulated in each brain region in adult male rat and emphasize marked differences in HMGR and low-density lipoprotein receptor regulation. The results provide new insights into the intricate network that regulates cholesterol homoeostasis in the adult CNS in connection with the regional needs of this molecule. [ABSTRACT FROM AUTHOR]

Aim To elucidate the abnormality of vagal control in spontaneously hypertensive rats ( SHR) by measuring left ventricular myocardial interstitial acetylcholine ( ACh) release in response to α2-adrenergic stimulation as an index of in vivo vagal nerve activity. Methods A cardiac microdialysis technique was applied to the rat left ventricle in vivo, and the effect of α2-adrenergic stimulation by medetomidine or electrical vagal nerve stimulation on myocardial interstitial ACh levels was examined in normotensive Wistar-Kyoto rats ( WKY) and SHR under anaesthetized conditions. Results Intravenous medetomidine (0.1 mg kg−1) significantly increased the ACh levels in WKY (from 2.4 ± 0.6 to 4.2 ± 1.3 nmol L−1, P < 0.05, n = 7) but not in SHR (from 2.5 ± 0.7 to 2.7 ± 0.7 nmol L−1, n = 7). In contrast, electrical vagal nerve stimulation increased the ACh levels in both WKY (from 1.0 ± 0.4 to 2.9 ± 0.9 nmol L−1, P < 0.001, n = 6) and SHR (from 0.9 ± 0.2 to 2.2 ± 0.4 nmol L−1, P < 0.001, n = 6). Intravenous administration of medetomidine (0.1 mg kg−1) did not affect the vagal nerve stimulation-induced ACh release in either WKY or SHR. Conclusion Medetomidine-induced central vagal activation was impaired in SHR, whereas peripheral vagal control of ACh release was preserved. In addition to abnormal sympathetic control, vagal control by the central nervous system may be impaired in SHR. [ABSTRACT FROM AUTHOR]

Aim: This study was to determine the roles of inflammatory cytokines in paraventricular nucleus (PVN) in modulating sympathetic activity, blood pressure and cardiac sympathetic afferent reflex (CSAR). Methods: Renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) were recorded in anaesthetized rats with bilateral sinoaortic denervation and vagotomy. The CSAR was evaluated by the RSNA response to epicardial application of bradykinin (BK). The levels of inflammatory cytokines were measured with ELISA. Results: The PVN microinjection of pro-inflammatory cytokines (PIC), tumour necrosis factor (TNF)-α or interleukin (IL)-1β, increased the baseline MAP and RSNA, and enhanced the CSAR. Anti-inflammatory cytokines (AIC), IL-4 or IL-13, in the PVN only increased the baseline MAP. In the rats pretreated with TNF-α or IL-1β but not in the rats pretreated with IL-4 or IL-13, sub-response dose of angiotensin II caused significant increases in the MAP and RSNA and enhancement in the CSAR. AT1 receptor antagonist losartan in the PVN attenuated the effects of angiotensin II, TNF-α and IL-1β, but not the effects of IL-4 and IL-13. Stimulation of cardiac sympathetic afferents with epicardial application of BK increased the levels of TNF-α, IL-1β but not IL-4 in the PVN. Conclusion: TNF-α or IL-1β in the PVN increases blood pressure and sympathetic outflow and enhances the CSAR, which is partially dependent on the AT1 receptors, while IL-4 or IL-13 in the PVN only increases blood pressure. There is a synergetic effect of Ang II with TNF-α or IL-1β on blood pressure, sympathetic activity and CSAR. [ABSTRACT FROM AUTHOR]

Changes in skeletal muscle morphology and metabolism are associated with limited functional capacity in heart failure, which can be attenuated by neuromuscular electrical stimulation (ES). The purpose of the present study was to analyse the effects of ES upon GLUT-4 protein content, fibre structure and vessel density of the skeletal muscle in a rat model of HF subsequent to myocardial infarction. Forty-four male Wistar rats were assigned to one of four groups: sham (S), sham submitted to ES (S+ES), heart failure (HF) and heart failure submitted to ES (HF+ES). The rats in the ES groups were submitted to ES of the left leg during 20 days (2.5 kHz, once a day, 30 min, duty cycle 50%- 15 s contraction/15 s rest). After this period, the left tibialis anterior muscle was collected from all the rats for analysis. HF+ES rats showed lower values of lung congestion when compared with HF rats ( P = 0.0001). Although muscle weight was lower in HF rats than in the S group, thus indicating hypotrophy, 20 days of ES led to their recovery ( P < 0.0001). In both groups submitted to ES, there was an increase in muscle vessel density ( P < 0.04). Additionally, heart failure determined a 49% reduction in GLUT-4 protein content ( P < 0.03), which was recovered by ES ( P < 0.01). In heart failure, ES improves morphological changes and raises GLUT-4 content in skeletal muscle. [ABSTRACT FROM AUTHOR]

Caffeine activates 5′AMP-activated protein kinase (AMPK), a signalling intermediary implicated in the regulation of glucose, lipid and energy metabolism in skeletal muscle. Skeletal muscle expresses two catalytic α subunits of AMPK, α1 and α2, but the isoform specificity of caffeine-induced AMPK activation is unclear. The aim of this study was to determine which α isoform is preferentially activated by caffeine in vitro and in vivo using rat skeletal muscle. Rat epitrochlearis muscle was isolated and incubated in vitro in the absence or presence of caffeine. In another experiment, the muscle was dissected after intravenous injection of caffeine. Isoform-specific AMPK activity, the phosphorylation status of AMPKα Thr and acetyl-CoA carboxylase (ACC) Ser, the concentrations of ATP, phosphocreatine (PCr) and glycogen, and 3- O-methyl--glucose (3MG) transport activity were estimated. Incubation of isolated epitrochlearis muscle with 1 m of caffeine for 15 min increased AMPKα1 activity, but not AMPKα2 activity; concentrations of ATP, PCr and glycogen were not affected. Incubation with 3 m of caffeine activated AMPKα2 and reduced PCr and glycogen concentrations. Incubation with 1 m of caffeine increased the phosphorylation of AMPK and ACC and enhanced 3MG transport. Intravenous injection of caffeine (5 mg kg) predominantly activated AMPKα1 and increased 3MG transport without affecting energy status. Our results suggest that of the two α isoforms of AMPK, AMPKα1 is predominantly activated by caffeine via an energy-independent mechanism and that the activation of AMPKα1 increases glucose transport and ACC phosphorylation in skeletal muscle. [ABSTRACT FROM AUTHOR]

Non-steroidal anti-inflammatory drugs (NSAIDs) are effective in the treatment of various human diseases. However, these drugs also have serious adverse effects in the gastrointestinal tract. In the duodenum NSAIDs inhibit mucosal alkaline secretion (DMAS), an important protective mechanism against the acid emptied from the stomach in most species, including humans. Surprisingly, NSAIDs have been shown to stimulate DMAS in an anaesthetized rat model. The aim of this review was to summarize the effects of NSAIDs and selective cyclooxygenase-2 (COX-2) inhibition on duodenal function in the rat and provide an explanation for why these drugs stimulate DMAS. Included are new data examining the effect of α-adrenergic drugs on duodenal motility and DMAS. Experiments were performed in anaesthetized rats. The proximal duodenum was perfused luminally with an isotonic NaCl solution. DMAS, motility, fluid flux and epithelial permeability were assessed in the absence and presence of various COX inhibitors. COX inhibition induced duodenal motility, increased DMAS and augmented the sensitivity as well as the maximal response of the duodenal mucosa to lidocaine- or hypotonicity-induced increases in mucosal permeability. Furthermore, the ability of the duodenum to absorb water and to adjust osmolality in response to luminal hypotonicity was improved in COX-inhibited animals. These improvements are mediated predominately via inhibition of COX-2. Inhibition of COX-2 in rats with postoperative duodenal ileus induces muscle contractions, which in turn activate a nicotinic receptor-dependent intramural reflex that stimulates duodenocytes to increase the activity of apical Cl/HCO exchangers, resulting in a rise in DMAS. [ABSTRACT FROM AUTHOR]

Aim: Intestinal pressure differences or experimental distension induce ion secretion via the enteric nervous system, the sensorial origin of which is only poorly understood. This study aimed to investigate sensorial inputs and the role of afferent and interneurones in mechanically activated submucosal secretory reflex circuits. Methods: Distension-induced rheogenic chloride secretion was measured as increase in short-circuit current 10 min after distension (Δ ISC10; distension parameters ± 100 μL, 2 Hz, 20 s) in partially stripped rat distal colon in the Ussing-chamber in vitro. PGE2 and PGI2 were measured by radioimmunoassay. Results: Δ ISC10 was 2.0 ± 0.2 μmol h−1 cm−2 and could be attenuated by lobeline, mecamylamine and dimethylphenylpiperazine, indicating an influence of nicotinergic interneurones. Additionally, a contribution of afferent neurones was indicated from the short-term potentiation of Δ ISC10 by capsaicin (1 μm). As evidence for its initial event, indomethacin (1 μm) inhibited distension-induced secretion and the release of PGI2 was directly detected after distension. Furthermore, serotoninergic mediation was confirmed by granisetron (100 μm) which was functionally localized distally to PGI2 in this reflex circuit, as granisetron inhibited an iloprost-induced ISC, while indomethacin did not affect serotonin-activated ion secretion. Conclusions: Distension-induced active electrogenic chloride secretion in rat colon is mediated by a neuronal reflex circuit which includes afferent neurones and nicotinergic interneurones. It is initiated by distension-induced PGI2 release from subepithelial cells triggering this reflex via serotoninergic 5-HT3 receptor transmission. Functionally, this mechanism may help to protect against intestinal stasis but could also contribute to luminal fluid loss, e.g. during intestinal obstruction. [ABSTRACT FROM AUTHOR]

Aim: Orexin-producing neurones, located primarily in the perifornical region of the lateral hypothalamus, project to a wide spectrum of brain sites where they influence numerous behaviours as well as modulating the neuroendocrine and autonomic responses to stress. While some of the actions of orexin appear to be mediated via the type 1 receptor, some are not, including its action on the release of one stress hormone, prolactin. We describe here the ability of orexin to increase locomotor behaviours and identify the importance of both receptor subtypes in these actions. Methods: Rats were tested for their behavioural responses to the central activation of both the type 1 (OX1R) and type 2 (OX2R) receptor (ICV orexin A), compared to OX2R activation using a relatively selective OX2R agonist in the absence or presence of an orexin receptor antagonist that possesses highest affinity for OX1R. Results: Increases in locomotor activity were observed, effects which were expressed by not only orexin A, which binds to both the OX1R and the OX2R receptors, but also by the relatively selective OX2R agonist [(Ala11, Leu15)-orexin B]. Furthermore, the OX1R selective antagonist only partially blocked the action of orexin A on most locomotor behaviours and did not block the actions of [(Ala11, Leu15)-orexin B]. Conclusion: We conclude that orexin A exerts its effects on locomotor behaviour via both the OX1R and OX2R and that agonism or antagonism of only one of these receptors for therapeutic purposes (i.e. sleep disorders) would not provide selectivity in terms of associated behavioural side effects. [ABSTRACT FROM AUTHOR]

Aim: The aim of the present study was to investigate whether reactive oxygen species (ROS) in rostral ventrolateral medulla (RVLM) modulate cardiac sympathetic afferent reflex (CSAR) and the enhanced CSAR response caused by microinjection of angiotensin II (Ang II) into the paraventricular nucleus (PVN). Methods: Under urethane and α-chloralose anaesthesia, renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) were recorded in sinoaortic-denervated and cervical-vagotomized rats. The CSAR was evaluated by the RSNA response to epicardial application of capsaicin (1.0 nmol). Results: Bilateral RVLM microinjection of tempol (a superoxide anion scavenger) or polyethylene glycol-superoxide dismutase (PEG-SOD, an analogue of endogenous superoxide dismutase) attenuated the CSAR, but did not cause significant change in baseline RSNA and MAP. NAD(P)H oxidase inhibitors apocynin or phenylarsine oxide (PAO) also showed similar effects, but SOD inhibitor diethyldithio-carbamic acid (DETC) enhanced the CSAR and baseline RSNA, and increased the baseline MAP. Bilateral PVN microinjection of Ang II (0.3 nmol) enhanced the CSAR and increased RSNA and MAP, which was inhibited by the pre-treatment with RVLM administration of tempol, PEG-SOD, apocynin or PAO. The pre-treatment with DETC in the RVLM only showed a tendency in potentiating the CSAR response of Ang II in the PVN, but significantly potentiated the RSNA and MAP responses of Ang II. Conclusion: These results suggest that the NAD(P)H oxidase-derived ROS in the RVLM modulate the CSAR. The ROS in the RVLM is necessary for the enhanced CSAR response caused by Ang II in the PVN. [ABSTRACT FROM AUTHOR]

Aim: Few dietary studies have looked beyond fish oil to explain the beneficial metabolic effects of a fish-containing diet. Our aim was to study whether addition of herring, or sub-fractions of herring, could counteract negative metabolic effects known to be induced by a high-fat, high-sugar diet. Methods: Rats were given six different diets: standard pellets; high energy diet with chicken mince (HiE control); high energy diet with herring mince (HiE herring); and high energy diet with chicken mince and either herring oil (HiE herring oil), herring press juice, PJ (HiE PJ) or herring low molecular weight PJ (HiE LMW-PJ). Factors associated with the metabolic syndrome were measured. Results: There were no differences in energy intake or body weight between the groups, but animals fed high energy diets had a higher body fat content compared with the pellet group, although not statistically significant in all groups. Mesenteric adipocyte size was smaller in the HiE herring oil group compared with the HiE control. Glucose clamp studies showed that, compared with the pellet group, the HiE control and HiE herring diets, but not the HiE herring oil diet, induced insulin resistance. Addition of herring or herring oil to the high energy diet decreased total cholesterol levels, triacylglycerols and the atherogenic index compared with the HiE control group. Conclusions: The results suggest that addition of herring or herring oil counteracts negative effects on blood lipids induced by a high energy diet. The lipid component of herring thus seems to be responsible for these beneficial effects. [ABSTRACT FROM AUTHOR]

Aim: Activated satellite cells (SCs) have the ability to reacquire a quiescent, undifferentiated state. Pax7 plays a crucial role in allowing activated SCs to undergo self-renewal. Because the increase in the SC population is induced during overload-induced skeletal muscle hypertrophy, it is possible that Pax7-regulated SC self-renewal is involved in the modulation of the SC population during the functional overload of skeletal muscles. However, the characteristics of the expression patterns of Pax7 in SCs during the functional overload of adult skeletal muscles are poorly understood. Methods: Using immunohistochemical approaches, we examined the temporal and spatial expression patterns of Pax7 expressed in SCs during the functional overloading of rat skeletal muscles. Results: The time course of Pax7 expression in SCs was similar to that of the expression of the differentiation regulatory factor myogenin during the early stage of functional overload. However, the percentage of SCs that expressed Pax7 was markedly higher than that of the SCs that expressed myogenin. Coexpression of Pax7 and myogenin was not detected in SCs. In addition, the expression of cyclin-dependent kinase inhibitor p21, which regulates cell cycle arrest and differentiation, was not detected in Pax7-positive SCs. Conclusion: These results suggest that Pax7-regulated self-renewal of SCs may be induced during the early stage of functional overload and may contribute to modulating the SC population in hypertrophied muscles. Furthermore, it was suggested that the numbers of SCs which underwent self-renewal may be higher than that of SCs which were provided as the additional myonuclei for hypertrophying myofibres. [ABSTRACT FROM AUTHOR]

Aim: We aimed at gaining more insight into the mechanisms underlying exercise-induced alterations in myocardial ceramide (CER) content by employing physical activity of various durations and examining all key pathways of CER metabolism. Methods: The experiments were carried out on male Wistar rats divided into four groups ( n = 6 in each case): control, exercised for 30 and 90 min and until exhaustion on the electrically driven treadmill moving with a speed of 1200 m h−1 and set at +10° incline. The animals were anaesthetized and samples of the heart’s left ventricle were excised. Results: Thirty-minute exercise decreased the level of CER in the heart by 15%. However, after 90 min of running it returned to the baseline and at the point of exhaustion it exceeded that of the control animals by 26%. The initial reduction in the content of CER was probably a result of its augmented degradation, as a concomitant elevation in the activity of acid ceramidase and the level of sphingosine was observed. The transition from reduction in CER content after 30 min of exercise to its accumulation at the point of exhaustion was a consequence of gradual reduction in the activity of acid ceramidase and simultaneous increase in the rate of de novo CER synthesis, as evidenced by progressive activation of serine palmitoyltransferase and accumulation of sphinganine. Conclusion: We conclude that the effect of physical effort on myocardial CER content and metabolism depends to a large extent on exercise duration. [ABSTRACT FROM AUTHOR]

Aim: Uroguanylin and guanylin are endogenous ligands for guanylate cyclase C, an upstream regulator of the cystic fibrosis transmembrane resistance (CFTR) anion channel, and both peptides increase intestinal anion export in vitro. We have compared the effects of close intra-arterial and luminal administration of uroguanylin and guanylin on duodenal bicarbonate secretion in vivo and studied the interactions with melatonin and cholinergic stimulation. Methods: Lewis × Dark Agouti rats were anaesthetized and a segment of the proximal duodenum with intact blood supply was cannulated in situ. Mucosal bicarbonate secretion (pH stat) was continuously recorded and peptides were infused intra-arterially or added to the luminal perfusate. Results: Intra-arterial (50–1000 pmol kg−1 h−1) as well as luminal administration (50–500 nmol L−1) of guanylin or uroguanylin caused dose-dependent increases in the duodenal secretion. Luminal administration induced more rapidly appearing rises in secretion and the two peptides induced secretory responses of similar shape and magnitude. The melatonin MT2-selective antagonist luzindole (600 nmol kg−1) significantly depressed the response to intra-arterial guanylins but did not affect secretion induced by luminal guanylins. Similarly, the muscarinic antagonist atropine (0.75 μmol kg−1 followed by 0.15 μmol kg−1 h−1) abolished the response to intra-arterial uroguanylin but caused only slight suppression of the response to luminal uroguanylin. Conclusions: Intra-arterial as well as luminal uroguanylin and guanylin are potent stimuli of duodenal mucosal bicarbonate secretion in vivo. The response to luminal guanylins reflects an action at apical receptors. Stimulation by parenteral guanylins, in contrast, is under cholinergic influence and interacts with melatonin produced by mucosal enteroendocrine cells. [ABSTRACT FROM AUTHOR]

Introduction: Vasopressin (AVP) stimulates sodium reabsorption and Na,K,2Cl-cotransporter (NKCC2) protein level in the thick ascending limb (TAL) of Henle's loop in rats. Rats with congestive heart failure (CHF) have increased protein level of NKCC2, which can be normalized by angiotensin II receptor type-1 (AT1) blockade with losartan. Aim: In this study, we investigated whether CHF rats displayed changes in AVP stimulated cAMP formation in the TAL and examined the role of AT1 receptor blockade on this system. Method: CHF was induced by ligation of the left anterior descending coronary artery (LAD). SHAM-operated rats were used as controls. Half of the rats were treated with losartan (10 mg kg day−1 i.p.). Results: CHF rats were characterized by increased left ventricular end diastolic pressure. Measurement of cAMP in isolated outer medullary TAL showed that both basal and AVP (10−6 m) stimulated cAMP levels were significantly increased in CHF rats (25.52 ± 4.49 pmol cAMP μg−1 protein, P < 0.05) compared to Sham rats (8.13 ± 1.14 pmol cAMP μg−1 protein), P < 0.05). Losartan significantly reduced the basal level of cAMP in CHF rats (CHF: 12.56 ± 1.93 fmol μg−1 protein vs. Los-CHF: 7.49 ± 1.08, P < 0.05), but not in Sham rats (SHAM: 4.66 ± 0.59 vs. Los-SHAM: 4.75 ± 0.71). AVP-mediated cAMP accumulation was absent in both groups treated with losartan (Los-SHAM: 4.75 ± 0.71 and Los-CHF: 7.49 ± 1.08). Conclusion: The results indicate that the increased NKCC2 protein level in the mTAL from CHF rats is associated with increased cAMP accumulation in this segment. Furthermore, the finding that AT1 receptor blockade prevents AVP-mediated cAMP accumulation in both SHAM and CHF rats suggests an interaction between angiotensin II and AVP in regulation of mTAL Na reabsorption. [ABSTRACT FROM AUTHOR]

Aim: Whereas prostaglandin E2 has been characterized as the principal vasodepressor lipid, medullipin remains a hypothetical vasodepressor principle of the renal medulla. Representing the first step towards the isolation of medullipin as a pure compound, the aim of the present study was to determine whether or not the known vasodilator and antihypertensive action of prostaglandins play a role in the antihypertensive activity of renal medulla. Methods: A chloroform extract of porcine kidney medulla was fractionated by gradient vacuum liquid chromatography (VLC) and analysed by capillary GC-MS for the presence of prostaglandins (detection limit: 2.2 ppm). The biological activity was determined in spontaneously hypertensive Wistar rats. The particle size of injectable colloids prepared from extract and fractions was controlled by photon correlation spectroscopy. Results: The extract caused a pronounced blood pressure decline (29.6 ± 6.3/24.9± 5.5 mmHg; P = 0.0078; 10 mg kg−1 body weight; particle size of 143 ± 18 nm; n = 7) lasting for more than 1 h. The heart rate remained stable, showing only a slightly decrease. All fractions were shown to be devoid of vasodilator prostanoid substances. The VLC procedure allowed the successful separation of endogenous emulsifiers from the active principle. An extract from the renal cortex did not exhibit a similar vasodepressor effect. Conclusion: Prostaglandins are excluded as the blood pressure-lowering active principle of a total lipid kidney medulla extract. The vasodepressor principle is contained in the kidney medulla, but not in the cortex. It can be separated from endogenous emulsifying substances, is chromatographically stable, and is amenable to purification and chemical characterization. [ABSTRACT FROM AUTHOR]

The article discusses obesity-related hypertension, particularly on the baroreceptor resetting related to chronic arterial hypertension and the recommended pharmacological strategy to treat the disease. Also cited are the effectiveness of calcineurin phosphatase inhibitor-type immunosuppressant tacrolimus in restoring baroreceptor sensitivity, how the arterial baroreceptors adapt to elevated blood pressure, and the study by S. A. Khan and colleagues on obesity-induced hypertension in rats.

The article discusses how obesity can alter the automatic control of cardiovascular system. Topics discussed include obesity leading to activation of the sympathetic nervous system, evidence of altered baroreceptor function in obesity by taking rats as experimental animals, and increase in renal interstitial hydrostatic pressure with retroperitoneal fat mass.

The article provides information on a study that examined the pericyte hypothesis in rats. The researchers tested the process by simultaneous administration of two different antiapoptotic drugs which abolished the effect of losartan on pericyte number. Based on the results, they concluded that transient angiotensin II receptor blocked the late medullary effects in immature hypertensive rats.