The aim of this study was to investigate nitric oxide (NO) production and L-NAME-sensitive component of endothelium-dependent vasorelaxation in adult normotensive Wistar-Kyoto rats (WKY), borderline hypertensive rats (BHR) and spontaneously hypertensive rats (SHR). Blood pressure (BP) of WKY, BHR and SHR (determined by tail-cuff) was 111+/-3, 140+/-4 and 184+/-6 mm Hg, respectively. NO synthase activity (determined by conversion of [(3)H]-L-arginine) was significantly higher in the aorta of BHR and SHR vs. WKY and in the left ventricle of SHR vs. both BHR and WKY. L-NAME-sensitive component of endothelium-dependent relaxation was investigated in the preconstricted femoral arteries using the wire myograph during isometric conditions as a difference between acetylcholine-induced relaxation before and after acute N(G)-nitro-L-arginine methyl ester pre-treatment (L-NAME, 10(-5) mol/l). Acetylcholine-induced vasorelaxation of SHR was significantly greater than that in WKY. L-NAME-sensitive component of vasorelaxation in WKY, BHR and SHR was 20+/-3 %, 29+/-4 % (p<0.05 vs. WKY) and 37+/-3 % (p<0.05 vs. BHR), respectively. There was a significant positive correlation between BP and L-NAME-sensitive component of relaxation of the femoral artery. In conclusion, results suggest the absence of endothelial dysfunction in the femoral artery of adult borderline and spontaneously hypertensive rats and gradual elevation of L-NAME-sensitive component of vasorelaxation with increasing blood pressure.

• MeSH
• acetylcholin farmakologie   MeSH
• aorta účinky léků   enzymologie   MeSH
• arteria femoralis účinky léků   patofyziologie   MeSH
• hypertenze genetika   metabolismus   patofyziologie   MeSH
• inhibitory enzymů farmakologie   MeSH
• krevní tlak * MeSH
• krysa rodu rattus MeSH
• modely nemocí na zvířatech MeSH
• NG-nitroargininmethylester farmakologie   MeSH
• oxid dusnatý metabolismus   MeSH
• potkani inbrední SHR MeSH
• potkani inbrední WKY MeSH
• srdeční komory účinky léků   enzymologie   MeSH
• stupeň závažnosti nemoci MeSH
• synthasa oxidu dusnatého antagonisté a inhibitory   metabolismus   MeSH
• vazodilatace účinky léků   MeSH
• vazodilatancia farmakologie   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• Klíčová slova
• PROVINOL,
• MeSH
• arteria femoralis fyziologie   metabolismus   MeSH
• cévní endotel metabolismus   MeSH
• fenoly farmakologie   MeSH
• finanční podpora výzkumu jako téma MeSH
• krysa rodu rattus MeSH
• oxid dusnatý fyziologie   MeSH
• vazodilatace fyziologie   MeSH
• víno využití   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• zvířata MeSH

N(G)-nitro-L-arginine methyl ester (L-NAME) is a non-specific nitric oxide (NO) synthase inhibitor, commonly used for the induction of NO-deficient hypertension. The aim of this study was to investigate the effect of chronic low-dose administration of L-NAME on NO production, vascular function and structure of the heart and selected arteries of rats. Adult male Wistar rats were treated with L-NAME in the dose of approximately 1.5 mg/kg/day in drinking water for 8 weeks. Basal blood pressure (BP) of rats (determined by tail-cuff) was 112+/-3 mm Hg. The low-dose administration of L-NAME significantly elevated BP measured on the third and sixth week of treatment vs. controls by approximately 9 % and 12 %, respectively. After this period, BP of L-NAME-treated rats returned to the control values. The relative left ventricular mass, heart fibrosis and collagen III/collagen I ratio were not affected by L-NAME. Similarly, there were no alterations in the cross-sectional area and wall thickness/diameter ratio of the aorta and the femoral artery of L-NAME-treated rats. NO synthase activity (determined by conversion of [(3)H]-L-arginine to [(3)H]-L-citrulline) was not altered in the hypothalamus of L-NAME-treated rats. Interestingly, chronic low-dose L-NAME treatment significantly elevated NO synthase activity in the left ventricle and aorta, increased endothelium-dependent acetylcholine-induced vasorelaxation and reduced serotonin-induced vasoconstriction of the femoral artery. The data suggest that chronic low-dose L-NAME treatment can increase NO production and vasorelaxation in normotensive rats without negative structural changes in the cardiovascular system.

• MeSH
• acetylcholin farmakologie   MeSH
• aorta účinky léků   enzymologie   MeSH
• aplikace orální MeSH
• arteria femoralis účinky léků   MeSH
• časové faktory MeSH
• hypothalamus účinky léků   enzymologie   MeSH
• inhibitory enzymů aplikace a dávkování   farmakologie   MeSH
• krevní tlak účinky léků   MeSH
• krysa rodu rattus MeSH
• NG-nitroargininmethylester aplikace a dávkování   farmakologie   MeSH
• oxid dusnatý metabolismus   MeSH
• potkani Wistar MeSH
• serotonin farmakologie   MeSH
• srdeční komory účinky léků   enzymologie   MeSH
• synthasa oxidu dusnatého antagonisté a inhibitory   metabolismus   MeSH
• upregulace MeSH
• vazodilatace účinky léků   MeSH
• vazodilatancia farmakologie   MeSH
• vazokonstriktory farmakologie   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

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.

• MeSH
• arteriae mesentericae MeSH
• cévní endotel metabolismus   MeSH
• krysa rodu rattus MeSH
• nitroprusid farmakologie   MeSH
• oxid dusnatý * metabolismus   MeSH
• vazodilatace * MeSH
• vazokonstrikce MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

• Publikační typ
• abstrakty MeSH

• MeSH
• agonisté vápníkových kanálů aplikace a dávkování   terapeutické užití   MeSH
• krysa rodu rattus MeSH
• modely nemocí na zvířatech MeSH
• plicní hypertenze farmakoterapie   MeSH
• vazodilatancia terapeutické užití   MeSH
• vazokonstrikce účinky léků   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH

• Klíčová slova
• PROVINOL,
• MeSH
• arteria femoralis účinky léků   MeSH
• finanční podpora výzkumu jako téma MeSH
• krysa rodu rattus MeSH
• vazodilatace účinky léků   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• zvířata MeSH

• Publikační typ
• abstrakty MeSH

• MeSH
• agonisté adrenergních beta-receptorů farmakologie   MeSH
• arginin farmakologie   MeSH
• arterie fyziologie   MeSH
• isoprenalin farmakologie   MeSH
• krysa rodu rattus MeSH
• synthasa oxidu dusnatého antagonisté a inhibitory   fyziologie   MeSH
• vazodilatace fyziologie   účinky léků   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• zvířata MeSH
• Publikační typ
• srovnávací studie MeSH

Several non-aromatic substituted oxime derivatives (formamidoxime, acetaldoxime, acetone oxime, acetohydroxamic acid, formaldoxime) function as vasorelaxant NO donors when added to precontracted aortic rings in vitro. This study was aimed to evaluate whether these substances posses vasodilator properties under in vivo conditions. We studied blood pressure changes elicited by administration of these compounds to conscious chronically catheterized Wistar rats in which endogenous NO synthesis was acutely inhibited by N(omega)-nitro-L-arginine methyl ester (L-NAME) pretreatment (30 mg/kg i.v.). Three of the tested substances (formaldoxime, acetohydroxamic acid and formamidoxime) induced pronounced dose-dependent blood pressure reduction which was further augmented when baroreflex operation was interrupted by ganglionic blockade (5 mg/kg pentolinium). Pretreatment of rats with methylene blue (soluble guanylate cyclase inhibitor) was used to estimate the contribution of NO to observed blood pressure lowering effects of the above compounds. Nitric oxide seems to be responsible for the entire formaldoxime-induced blood pressure decrease and for a considerable part of blood pressure changes elicited by formamidoxime. On the contrary, we did not find a significant NO contribution to blood pressure reduction caused by acetohydroxamic acid. In conclusion, our study confirmed in vivo vasodilator effects of three above mentioned compounds which were earlier demonstrated to induce in vitro vasorelaxation. It indicated a variable contribution of nitric oxide to blood pressure changes elicited by particular compounds. Substances with hydrophilic character (formamidoxime, acetohydroxamic acid, formaldoxime) were effective, whereas less hydrophilic substance (acetaldoxime) or slightly hydrophobic one (acetone oxime) were ineffective.

• MeSH
• aorta fyziologie   účinky léků   MeSH
• financování organizované MeSH
• hydrofobní a hydrofilní interakce MeSH
• inhibitory enzymů farmakologie   MeSH
• krevní tlak fyziologie   účinky léků   MeSH
• krysa rodu rattus MeSH
• kyseliny hydroxamové MeSH
• NG-nitroargininmethylester farmakologie   MeSH
• oxid dusnatý fyziologie   MeSH
• oximy farmakologie   MeSH
• pentoliniumtartrát farmakologie   MeSH
• potkani Wistar MeSH
• vazodilatace fyziologie   účinky léků   MeSH
• vazodilatancia farmakologie   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH