Exercise training (ET) is well established to induce vascular adaptations on the metabolically active muscles. These adaptations include increased function of vascular potassium channels and enhanced endothelium-dependent relaxations. However, the available data on the effect of ET on vasculatures that normally constrict during exercise, such as mesenteric arteries (MA), are scarce and not conclusive. Therefore, this study hypothesized that 10 weeks of moderate-intensity ET would result in adaptations towards more vasoconstriction or/and less vasodilatation of MA. Young Fischer 344 rats were randomly assigned to a sedentary group (SED; n=24) or exercise training group (EXE; n=28). The EXE rats underwent a progressive treadmill ET program for 10 weeks. Isometric tensions of small (SED; 252.9+/-29.5 microm, EXE; 248.6+/-34.4 microm) and large (SED; 397.7+/-85.3 microm, EXE; 414.0+/-86.95 microm) MA were recorded in response to cumulative phenylephrine concentrations (PE; 0-30 microM) in the presence and absence of the BKCa channel blocker, Iberiotoxin (100 nM). In another set of experiments, tensions in response to cumulative concentration-response curves of acetylcholine (ACh) or sodium nitroprusside (SNP) were obtained, and pEC50s were compared. Immunoblotting was performed to measure protein expression levels of the BKCa channel subunits and eNOS. ET did not alter the basal tension of small and large MA but significantly increased their responses to PE, and reduced the effect of BKCa channels in opposing the contractile responses to PE without changes in the protein expression level of BKCa subunits. ET also elicited a size-dependent functional adaptations that involved reduced endothelium-independent and endothelium-dependent relaxations. In large MA the sensitivity to SNP was decreased more than in small MA suggesting impaired nitric oxide (NO)-dependent mechanisms within the vascular smooth muscle cells of ET group. Whereas the shift in pEC50 of ACh-induced relaxation of small MA would suggest more effect on the production of NO within the endothelium, which is not changed in large MA of ET group. However, the eNOS protein expression level was not significantly changed between the ET and SED groups. In conclusion, our results indicate an increase in contraction and reduced relaxation of MA after 10 weeks of ET, an adaptation that may help shunt blood flow to metabolically active tissues during acute exercise.
Being a chilling-sensitive staple crop, rice (Oryza sativa L.) is vulnerable to climate change. The competence of rice to withstand chilling stress should, therefore, be enhanced through technological tools. The present study employed chemical intervention like application of sodium nitroprusside (SNP) as nitric oxide (NO) donor and elucidated the underlying morpho-physiological and biochemical mechanisms of NO-mediated chilling tolerance in rice plants. At germination stage, germination indicators were interrupted by chilling stress (5.0 ± 1.0 °C for 8 h day-1), while pretreatment with 100 μM SNP markedly improved all the indicators. At seedling stage (14-day-old), chilling stress caused stunted growth with visible toxicity along with alteration of biochemical markers, for example, increase in oxidative stress markers (superoxide, hydrogen peroxide, and malondialdehyde) and osmolytes (total soluble sugar; proline and soluble protein content, SPC), and decrease in chlorophyll (Chl), relative water content (RWC), and antioxidants. However, NO application attenuated toxicity symptoms with improving growth attributes which might be related to enhance activities of antioxidants, mineral contents, Chl, RWC and SPC. Furthermore, principal component analysis indicated that water imbalance and increased oxidative damage were the main contributors to chilling injury, whereas NO-mediated mineral homeostasis and antioxidant defense were the critical determinants for chilling tolerance in rice. Collectively, our findings revealed that NO protects against chilling stress through valorizing cellular defense mechanisms, suggesting that exogenous application of NO could be a potential tool to evolve cold tolerance as well as climate resilience in rice.
- MeSH
- donory oxidu dusnatého farmakologie MeSH
- homeostáza účinky léků MeSH
- klíčení účinky léků MeSH
- malondialdehyd metabolismus MeSH
- nitroprusid farmakologie MeSH
- nízká teplota MeSH
- ochrana úrody metody MeSH
- oxid dusnatý metabolismus MeSH
- peroxid vodíku metabolismus MeSH
- peroxidace lipidů účinky léků MeSH
- peroxidasy metabolismus MeSH
- reakce na chladový šok fyziologie MeSH
- rýže (rod) účinky léků MeSH
- semenáček účinky léků MeSH
- superoxidy metabolismus MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Nitric oxide (NO) is a major gasotransmitter involved in several physiological processes of male reproduction. There is, nevertheless, little information concerning the role of NO during semen storage. The aim of this study was to evaluate the effect of NO on boar semen stored at 17oC for 72 h. For this purporse, sperm samples were treated with 0.625, 1.25, 2.5, 5, and 10 mM aminoguanidine (AG) or Nω-Nitro-L-arginine methyl ester hydrochloride (L-NAME), a selective and non-selective NO synthase (NOS) inhibitor, respectively. Moreover, sodium nitroprusside (SNP), a NO donor, was used at the dose of 18.75, 37.5, 75, and 150 μM. Sperm motility, membrane integrity, and acrosomal status were evaluated at 0, 4, 24, 48, and 72 h of semen storage. A significant increase of the amplitude of lateral sperm head displacement (ALH), and both curvilinear and straight-line velocity (VCL and VSL, respectively) was observed at 72 h of semen storage in samples treated with 0.625 mM AG, probably because of the antioxidant properties of this NOS inhibitor. Contrarily, 0.625 mM L-NAME showed no effect on boar sperm parameters during the entire period of semen storage. Moreover, AG and L-NAME at 10 mM negatively affected sperm kinetics and acrosome integrity, which may provide further support to the notion that low NO levels are necessary for a normal sperm function. The concentrations of SNP used in this study had mostly no or negative effects on boar sperm parameters during semen storage. In conclusion, the results from this study increase the understanding of the role of NO on boar sperm physiology.
- MeSH
- akrozom účinky léků MeSH
- buněčná membrána účinky léků MeSH
- časové faktory MeSH
- guanidiny farmakologie MeSH
- motilita spermií účinky léků MeSH
- nitroprusid farmakologie MeSH
- oxid dusnatý aplikace a dávkování farmakologie MeSH
- prasata * MeSH
- spermie účinky léků MeSH
- synthasa oxidu dusnatého, typ II antagonisté a inhibitory metabolismus MeSH
- uchování spermatu veterinární MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
The endothelial barrier function is tightly controlled by a broad range of signaling cascades including nitric oxide-cyclic guanosine monophosphate (NO-cGMP) pathway. It has been proposed that disturbances in NO and cGMP production could interfere with proper endothelial barrier function. In this study, we assessed the effect of interferon-gamma (IFN-gamma), a pro-inflammatory cytokine, on NO and cGMP levels and examined the mechanisms by which NO and cGMP regulate the IFN-gamma-mediated HUVECs hyperpermeability. The flux of fluorescein isothiocyanate-labeled dextran across cell monolayers was used to study the permeability of endothelial cells. Here, we found that IFN-gamma significantly attenuated basal NO concentration and the increased NO levels supplied by a NO donor, sodium nitroprusside (SNP). Besides, application of IFN-gamma also significantly attenuated both the basal cGMP concentration and the increased cGMP production donated by a cell permeable cGMP analogue, 8-bromo-cyclic GMP (8-Br-cGMP). In addition, exposure of the cell monolayer to IFN-gamma significantly increased HUVECs basal permeability. However, L-NAME pretreatment did not suppress IFN-gamma-induced HUVECs hyperpermeability. L-NAME pretreatment followed by SNP or SNP pretreatment partially reduced IFN-gamma-induced HUVECs hyperpermeability. Pretreatment with a guanylate cyclase inhibitor, 6-anilino-5,8-quinolinedione (LY83583), led to a further increase in IFN-gamma-induced HUVECs hyperpermeability. The findings suggest that the mechanism underlying IFN-gamma-induced increased HUVECs permeability is partly related to the inhibition of NO production.
- MeSH
- donory oxidu dusnatého farmakologie MeSH
- endoteliální buňky pupečníkové žíly (lidské) účinky léků metabolismus MeSH
- guanosinmonofosfát cyklický analogy a deriváty metabolismus farmakologie MeSH
- guanylátcyklasa antagonisté a inhibitory MeSH
- inhibitory enzymů farmakologie MeSH
- interferon gama farmakologie MeSH
- kapilární permeabilita účinky léků MeSH
- lidé MeSH
- NG-nitroargininmethylester farmakologie MeSH
- nitroprusid farmakologie MeSH
- oxid dusnatý metabolismus MeSH
- permeabilita buněčné membrány MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
STR/N is an inbred strain of mice which is known to exhibit extreme polydipsia and polyuria. We previously found central administration of angiotensin II enhanced cardiovascular responses in STR/N mice than normal mice, suggesting that STR/N mice might exhibit different cardiovascular responses. Therefore, in this study, we investigated daily mean arterial blood pressure and heart rate, and changes in the baroreceptor-heart rate reflex in conscious STR/N mice and control (ICR) mice. We found that variability in daily mean arterial blood pressure and heart rate was significantly larger in STR/N mice than in ICR mice (p<0.05). There was a stronger response to phenylephrine (PE) in STR/N mice than in ICR mice. For baroreceptor reflex sensitivity, in the rapid response period, the slopes of PE and sodium nitroprusside (SNP) were more negative in STR/N mice than in ICR mice. In the later period, the slopes of PE and SNP were negatively correlated between heart rate and blood pressure in ICR mice, but their slopes were positively correlated in STR/N mice. These results indicated that STR/N mice exhibited the different cardiovascular responses than ICR mice, suggesting that the dysfunction of baroreceptor reflex happened in conscious STR/N mice.
- MeSH
- baroreflex účinky léků MeSH
- fenylefrin farmakologie MeSH
- krevní tlak MeSH
- myši inbrední ICR MeSH
- myši MeSH
- nitroprusid farmakologie MeSH
- polydipsie genetika patofyziologie MeSH
- presoreceptory patofyziologie MeSH
- srdeční frekvence * účinky léků MeSH
- vazodilatancia farmakologie MeSH
- vazokonstriktory farmakologie MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Stellate ganglion blockade (SGB) with a local anesthetic increases muscle sympathetic nerve activity in the tibial nerve in humans. However, whether this sympathetic excitation in the tibial nerve is due to a sympathetic blockade in the neck itself, or due to infiltration of a local anesthetic to adjacent nerves including the vagus nerve remains unknown. To rule out one mechanism, we examined the effects of cervical sympathetic trunk transection on renal sympathetic nerve activity (RSNA) in anesthetized rats. Seven rats were anesthetized with intraperitoneal urethane. RSNA together with arterial blood pressure and heart rate were recorded for 15 min before and 30 min after left cervical sympathetic trunk transection. The baroreceptor unloading RSNA obtained by decreasing arterial blood pressure with administration of sodium nitroprusside was also measured. Left cervical sympathetic trunk transection did not have any significant effects on RSNA, baroreceptor unloading RSNA, arterial blood pressure, and heart rate. These data suggest that there was no compensatory increase in RSNA when cervical sympathetic trunk was transected and that the increase in sympathetic nerve activity in the tibial nerve during SGB in humans may result from infiltration of a local anesthetic to adjacent nerves rather than a sympathetic blockade in the neck itself.
- MeSH
- akční potenciály MeSH
- baroreflex účinky léků MeSH
- časové faktory MeSH
- financování organizované MeSH
- fyziologická adaptace MeSH
- ganglionektomie MeSH
- kosterní svaly inervace MeSH
- krevní tlak MeSH
- krysa rodu rattus MeSH
- ledviny inervace MeSH
- nervus tibialis fyziologie MeSH
- nitroprusid farmakologie MeSH
- potkani Sprague-Dawley MeSH
- srdeční frekvence MeSH
- sympatická ganglia fyziologie chirurgie MeSH
- vazodilatancia farmakologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
An increase in fetoplacental vascular resistance caused by hypoxia is considered one of the key factors of placental hypoperfusion and fetal undernutrition leading to intrauterine growth restriction (IUGR), one of the serious problems in current neonatology. However, although acute hypoxia has been shown to cause fetoplacental vasoconstriction, the effects of more sustained hypoxic exposure are unknown. This study was designed to test the hypothesis that chronic hypoxia elicits elevations in fetoplacental resistance, that this effect is not completely reversible by acute reoxygenation, and that it is accompanied by increased acute vasoconstrictor reactivity of the fetoplacental vasculature. We measured fetoplacental vascular resistance as well as acute vasoconstrictor reactivity in isolated perfused placentae from rats exposed to hypoxia (10% O(2)) during the last week of a 3-wk pregnancy. We found that chronic hypoxia shifted the relationship between perfusion pressure and flow rate toward higher pressure values (by approximately 20%). This increased vascular resistance was refractory to a high dose of sodium nitroprusside, implying the involvement of other factors than increased vascular tone. Chronic hypoxia also increased vasoconstrictor responses to angiotensin II (by approximately 75%) and to acute hypoxic challenges (by >150%). We conclude that chronic prenatal hypoxia causes a sustained elevation of fetoplacental vascular resistance and vasoconstrictor reactivity that are likely to produce placental hypoperfusion and fetal undernutrition in vivo.
- MeSH
- angiotensin II farmakologie MeSH
- cévní rezistence účinky léků MeSH
- chronická nemoc MeSH
- financování organizované MeSH
- gestační stáří MeSH
- hypoxie komplikace patofyziologie MeSH
- krevní tlak MeSH
- krysa rodu rattus MeSH
- modely nemocí na zvířatech MeSH
- nitroprusid farmakologie MeSH
- placentární oběh účinky léků MeSH
- potkani Wistar MeSH
- regionální krevní průtok MeSH
- růstová retardace plodu etiologie patofyziologie MeSH
- rychlost toku krve MeSH
- těhotenství MeSH
- vazodilatancia farmakologie MeSH
- vazokonstrikce účinky léků MeSH
- vazokonstriktory farmakologie MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- zvířata MeSH
Chronic volume overload (VO) on the left ventricle (LV) augments redox stress and activates matrix metalloproteinase (MMP) which causes the endocardial endothelial-myocyte (EM) disconnection leading to myocardial contractile dysfunction. VO-induced MMP-9 activation impairs cardiac functions, in part by endothelial endocardial apoptosis, but the role of MMP-9 on EM functions remains obscure. We conjecture that chronic VO activates MMP-9 and causes EM uncoupling. Arteriovenous fistula (AVF) was created in genetically identical wild type (WT) mice (FVB/NJ) and MMP-9 knockout mice (MMP-9KO, FVB.Cg-MMP9(tm1Tvu)/J). Sham-operated mice were used as controls. Before experimentation the phenotype analysis of MMP-9KO mice was carried out. In-gel-gelatin zymography for MMP-9 activation was performed on LV homogenates. The EM functions were determined on LV rings using tissue myobath. We report a decrease in MMP-9 activity in left ventricular myocardial extracts in MMP-9 deficient mice after AVF. The responses to drugs affecting cardiac functions (acetylcholine (Ach), nitroprusside and bradykinin) were attenuated in AVF mice suggesting the impairment of EM coupling. Interestingly, the EM functions were restored in the MMP-9 deficient mice after AVF. We suggest a direct cause-and-effect relationship between MMP-9 activation and EM uncoupling in LV myocardium after chronic VO and the possible involvement of MMP-9 in myocardial contractile performance.
- MeSH
- acetylcholin farmakologie MeSH
- aktivace enzymů MeSH
- arteriovenózní zkrat MeSH
- bradykinin farmakologie MeSH
- endoteliální buňky enzymologie účinky léků MeSH
- fenotyp MeSH
- financování organizované MeSH
- funkce levé komory srdeční účinky léků MeSH
- kontrakce myokardu účinky záření MeSH
- matrixová metaloproteinasa 9 genetika metabolismus nedostatek MeSH
- modely nemocí na zvířatech MeSH
- myokard enzymologie MeSH
- myši knockoutované MeSH
- myši MeSH
- nitroprusid farmakologie MeSH
- srdeční komory enzymologie patologie MeSH
- srdeční selhání enzymologie patofyziologie MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
Although the gastrointestinal tract is a rich source of melatonin and possesses numerous melatonin-binding sites, the role of melatonin in this tissue has not yet been fully elucidated. In this work we focused on the role of melatonin in the modulation of ion transport in rat distal colon. Whereas melatonin had no effect on colonic secretion or caused only infrequent and small changes in the short circuit current (Isc) due to its solvent ethanol, this mediator significantly modulated the secretion elicited by some secretagogues. Out of the five substances tested (prostaglandin E(2); 5-hydroxytryptamine; bethanechol; histamine; sodium nitroprusside) melatonin inhibited the effect of prostaglandin E(2) (PGE(2)) and sodium nitroprusside (SNP). Melatonin concentration-dependently decreased PGE(2)-evoked Isc and this inhibitory effect was more obvious from the mucosal side. The basal level of cAMP in colonic mucosa was not influenced by melatonin, but this drug prevented a PGE(2)-induced increase in the level of cAMP. The neurotoxin tetrodotoxin blocked the inhibitory effect of melatonin on SNP-induced Isc. Our data suggests that melatonin takes part in the modulation of colonic ion transport. The modulatory effect of melatonin on PGE(2)-induced Isc occurs directly at the level of the epithelium, whereas the effect on SNP-induced Isc is indirect and located in tetrodotoxin-sensitive enteric neurons.
- MeSH
- AMP cyklický fyziologie MeSH
- dinoproston farmakologie MeSH
- financování organizované MeSH
- iontový transport účinky léků MeSH
- kolon sekrece účinky léků MeSH
- krysa rodu rattus MeSH
- melatonin farmakologie MeSH
- nitroprusid farmakologie MeSH
- potkani Wistar MeSH
- receptor melatoninový MT1 fyziologie účinky léků MeSH
- tetrodotoxin farmakologie MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
Organické nitráty, stejně jako digitalis, patří i dnes k nepostradatelným lékům. Jako první je u anginy pectoris použil T. L. Brunton, Tate a Murrel, který roku 1879 publikoval práci o jeho aplikaci při angině pectoris. Záhy bylo potvrzeno, že účinným hemodynamickým mechanizmem amylnitritu a nitroglycerinu je vazodilatace, a to především ve venózním řečišti. Snížením venózního návratu klesá enddiastolický tlak a objem v levé i pravé komoře a spotřeba kyslíku v myokardu. William Osler byl první, kdo navrhl užití nitroglycerinu u pacientů se srdeční insuficiencí „je-li jejich pulz tvrdý“, jak píše v prvním vydání své knihy „Principles and Practice of Medicine“ z roku 1892. O padesát let později zjistil L. Goldberg ve dvojitě slepé studii, že izosorbid dinitrát snižuje zřetelně krevní tlak u hypertoniků. Izosorbid dinitrát a izosorbid 5-mononitrát jsou nyní – stejně jako nitroglycerin – užívány s úspěchem u nemocných s namáhavou i klidovou anginou pectoris a u některých nemocných se srdeční insuficiencí. Depotní formy, zejména izosorbid 5-mononitrátu se osvědčují v chronické léčbě ischemické choroby srdeční k prevenci anginózních záchvatů, aniž by vedly k toleranci. V článku jsou shrnuty též základy chemie a farmakologie organických nitrátů a nitroprusidu sodného, i zásady jejich užití v praxi. Je třeba znovu zvážit vhodnost podání depotních nitrátů u izolované systolické hypertenze starých lidí a kriticky posoudit jejich indikaci u nemocných s chronickou srdeční slabostí, zejména s ohledem na současnou konkomitantní léčbu.
Organic nitrates still constitute, like digitalis, an indispensable remedy. Amyl nitrite, discovered by Balard was the first to be used for the therapy of angina pectoris by Sir T. Lauder Brunton in 1867. Nitroglycerin (Glyceroltrinitrate) was synthetized by Ascanio Sobrero 1846 and was studied by Brunton, Tate, and Murrel who published his paper on the treatment of angina pectoris in 1879. It has been soon recognised that the main effect of nitrates is vasodilatation more pronounced in the veins, resulting in reduced venous return, decrease of left and right ventricular end-diastolic pressure and volume and in a reduction in the myocardioal oxygen demand. Sir William Osler was the first who suggested the use of nitroglycerin in patients with congestive heart failure „when the pulse is hard and firm“, in his „Principles and Practice of Medicine“ 1892. About fifty years later, L.Goldberg confirmed the antihypertensive effect of isosorbide dinitrate in a double – leticin trial on hypertensive patients. The longacting nitrates isosorbide dinitrate and isosorbide 5-mononitrate now share all the beneficial effects of nitroglycerin in patients with stable and unstable angina and in selected patients with heart failure. The sustained-release tablets of isosorbide 5-mononitrate have been shown to be effective with long-term use without inducing tolerance. The author also summaries basic data concerning the chemistry, pharmacology and clinical applications of organic nitrates and nitrocompounds. The position of nitrates in the treatment of isolated systolic hypertension in the elderly and of chronic heart failure is still to be established.
