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
• kondiční příprava zvířat MeSH
• krysa rodu Rattus MeSH
• nitroprusid farmakologie   MeSH
• oxid dusnatý * metabolismus   MeSH
• vápníkem aktivované draslíkové kanály s vysokou vodivostí - alfa-podjednotky metabolismus   MeSH
• vazodilatace * MeSH
• vazokonstrikce MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• Kcnma1 protein, rat MeSH Prohlížeč
• nitroprusid MeSH
• oxid dusnatý * MeSH
• vápníkem aktivované draslíkové kanály s vysokou vodivostí - alfa-podjednotky MeSH

The purpose of the present study was to assess the impact of brief daily reoxygenation during adaptation to chronic continuous hypoxia (CCH) on protective cardiac phenotype. Adult male Wistar rats were kept at CCH (10% oxygen) for 5, 15 or 30 days; a subgroup of animals was exposed to room air daily for a single 60-min period. While 5 days of CCH did not affect myocardial infarction induced by 20-min coronary artery occlusion and 3-h reperfusion, 15 days reduced infarct size from 62% of the area at risk in normoxic controls to 52%, and this protective effect was more pronounced after 30 days (41%). Susceptibility to ischemic ventricular arrhythmias exhibited reciprocal development. CCH increased myocardial abundance of mitochondrial superoxide dismutase (MnSOD) without affecting malondialdehyde concentration. Daily reoxygenation abolished both the infarct size-limiting effect of CCH and MnSOD upregulation, and increased malondialdehyde (by 53%). Ventricular cardiomyocytes isolated from CCH rats exhibited better survival and lower lactate dehydrogenase release caused by simulated ischemia/reperfusion than cells from normoxic and daily reoxygenated groups. The cytoprotective effects of CCH were attenuated by the large-conductance Ca2+-activated K+ (BKCa) channel blocker paxilline, while the opener NS1619 reduced cell injury in the normoxic group but not in the CCH group. Daily reoxygenation restored the NS1619- induced protection, whereas paxilline had no effect, resembling the pattern observed in the normoxic group. The results suggest that CCH is cardioprotective and brief daily reoxygenation blunts its salutary effects, possibly by a mechanism involving oxidative stress and attenuation of the activation of mitochondrial BKCa channels.

• MeSH
• draslíkové kanály metabolismus   MeSH
• glykosylace MeSH
• hypoxie metabolismus   MeSH
• kardiotonika farmakologie   MeSH
• krysa rodu Rattus MeSH
• kyslík metabolismus   MeSH
• malondialdehyd metabolismus   MeSH
• oxidační stres * MeSH
• potkani Wistar MeSH
• superoxiddismutasa metabolismus   MeSH
• vápníkem aktivované draslíkové kanály s vysokou vodivostí - alfa-podjednotky MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• draslíkové kanály MeSH
• kardiotonika MeSH
• Kcnma1 protein, rat MeSH Prohlížeč
• kyslík MeSH
• malondialdehyd MeSH
• superoxiddismutasa MeSH
• vápníkem aktivované draslíkové kanály s vysokou vodivostí - alfa-podjednotky MeSH

To investigate lisinopril effect on the contribution of nitric oxide (NO) and K(Ca) channels to acetylcholine (ACh)-induced relaxation in isolated mesenteric arteries of spontaneously hypertensive rats (SHRs). Third branch mesenteric arteries isolated from lisinopril treated SHR rats (20 mg/kg/day for ten weeks, SHR-T) or untreated (SHR-UT) or normotensive WKY rats were mounted on tension myograph and ACh concentration-response curves were obtained. Westernblotting of eNOS and K(Ca) channels was performed. ACh-induced relaxations were similar in all groups while L-NMMA and indomethacin caused significant rightward shift only in SHR-T group. Apamin and TRAM-34 (SK(Ca) and IK(Ca) channels blockers, respectively) significantly attenuated ACh-induced maximal relaxation by similar magnitude in vessels from all three groups. In the presence of L-NMMA, indomethacin, apamin and TRAM-34 further attenuated ACh-induced relaxation only in SHR-T. Furthermore, lisinopril treatment increased expression of eNOS, SK(Ca) and BK(Ca) proteins. Lisinopril treatment increased expression of eNOS, SK(Ca), BK(Ca) channel proteins and increased the contribution of NO to ACh-mediated relaxation. This increased role of NO was apparent only when EDHF component was blocked by inhibiting SK(Ca) and IK(Ca) channels. Such may suggest that in mesenteric arteries, non-EDHF component functions act as a reserve system to provide compensatory vasodilatation if (and when) hyperpolarization that is mediated by SK(Ca) and IK(Ca) channels is reduced.

• MeSH
• antihypertenziva farmakologie   MeSH
• arteriae mesentericae účinky léků   metabolismus   patofyziologie   MeSH
• blokátory draslíkových kanálů farmakologie   MeSH
• draslíkové kanály aktivované vápníkem účinky léků   metabolismus   MeSH
• hypertenze farmakoterapie   metabolismus   patofyziologie   MeSH
• inhibitory ACE farmakologie   MeSH
• lisinopril farmakologie   MeSH
• modely nemocí na zvířatech MeSH
• nízkovodivostní draslíkové kanály aktivované vápníkem účinky léků   metabolismus   MeSH
• oxid dusnatý metabolismus   MeSH
• potkani inbrední SHR MeSH
• potkani inbrední WKY MeSH
• signální transdukce účinky léků   MeSH
• synthasa oxidu dusnatého, typ III antagonisté a inhibitory   metabolismus   MeSH
• vápníkem aktivované draslíkové kanály s vysokou vodivostí - alfa-podjednotky účinky léků   metabolismus   MeSH
• vápníkem aktivované draslíkové kanály se střední vodivostí účinky léků   metabolismus   MeSH
• vazodilatace účinky léků   MeSH
• vazodilatancia farmakologie   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antihypertenziva MeSH
• blokátory draslíkových kanálů MeSH
• draslíkové kanály aktivované vápníkem MeSH
• inhibitory ACE MeSH
• Kcnma1 protein, rat MeSH Prohlížeč
• lisinopril MeSH
• nízkovodivostní draslíkové kanály aktivované vápníkem MeSH
• Nos3 protein, rat MeSH Prohlížeč
• oxid dusnatý MeSH
• synthasa oxidu dusnatého, typ III MeSH
• vápníkem aktivované draslíkové kanály s vysokou vodivostí - alfa-podjednotky MeSH
• vápníkem aktivované draslíkové kanály se střední vodivostí MeSH
• vazodilatancia MeSH

The aim of this study was to find out whether opening of mitochondrial large-conductance Ca(2+)-activated potassium channels (BK(Ca)) protects cardiomyocytes against injury caused by simulated ischemia and reperfusion. This study also aimed to determine whether the protective mechanism involves signaling by reactive oxygen species (ROS) and phosphatidylinositol-3-kinase (PI3K). We used isolated ventricular myocytes, which are believed to contain no functional BK(Ca) channels in the sarcolemma. Cells were isolated from the left ventricles of adult male Wistar rats and subjected to 25-min metabolic inhibition with NaCN and 2-deoxyglucose followed by 30-min re-energization. NS11021 (0.1 μmol/L), a novel BK(Ca) channel opener, or hydrogen peroxide (2 μmol/L) added at re-energization, increased cell survival (the number of rod-shaped cells) and markedly reduced the release of lactate dehydrogenase (LDH). These cytoprotective effects of NS11021 were completely abolished by paxilline, a BK(Ca) inhibitor, or tempol, an antioxidant, but not by wortmannin, an inhibitor of PI3K. NS11021 slightly but significantly increased the fluorescence signal in 2'7'-dichlorodihydrofluorescein diacetate (DCF-DA)-loaded myocytes, indicating an increased ROS formation. The NS11021-induced ROS formation was abolished by paxilline or tempol. NS13558 (0.1 μmol/L), an inactive structural analogue of NS11021, affected neither cell survival/LDH release nor DCF-DA fluorescence. These results suggest that pharmacological activation of mitochondrial BK(Ca) channels effectively protects isolated cardiomyocytes against injury associated with simulated reperfusion. The mechanism for this form of protection requires ROS signaling, but not the activation of the PI3K pathway.

• MeSH
• kardiomyocyty účinky léků   fyziologie   MeSH
• kardiovaskulární látky metabolismus   MeSH
• krysa rodu Rattus MeSH
• L-laktátdehydrogenasa analýza   MeSH
• peroxid vodíku metabolismus   MeSH
• potkani Wistar MeSH
• reperfuzní poškození myokardu patologie   prevence a kontrola   MeSH
• tetrazoly metabolismus   MeSH
• thiomočovina analogy a deriváty   metabolismus   MeSH
• vápníkem aktivované draslíkové kanály s vysokou vodivostí - alfa-podjednotky agonisté   metabolismus   MeSH
• viabilita buněk účinky léků   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• 1-(3,5-bis(trifluoromethyl)phenyl)-3-(4-bromo-2-(1H-tetrazol-5-yl)phenyl)thiourea MeSH Prohlížeč
• kardiovaskulární látky MeSH
• KCNMA1 protein, human MeSH Prohlížeč
• L-laktátdehydrogenasa MeSH
• peroxid vodíku MeSH
• tetrazoly MeSH
• thiomočovina MeSH
• vápníkem aktivované draslíkové kanály s vysokou vodivostí - alfa-podjednotky MeSH

Spontaneously hypertensive rats (SHR) are characterized by enhanced sympathetic vasoconstriction, whereas their vasodilator mechanisms are relatively attenuated compared to their high BP. The objective of our in vivo study was to evaluate whether the impaired function of BKCa and/or KV channels is responsible for abnormal cAMP-induced vasodilatation in genetic hypertension. Using conscious SHR and normotensive WKY rats we have shown that under the basal conditions cAMP overproduction elicited by the infusion of beta-adrenoceptor agonist (isoprenaline) caused a more pronounced decrease of baseline blood pressure (BP) in SHR compared to WKY rats. Isoprenaline infusion prevented BP rises induced by acute NO synthase blockade in both strains and it also completely abolished the fully developed BP response to NO synthase blockade. These cAMP-induced vasodilator effects were diminished by the inhibition of either BKCa or KV channels in SHR but simultaneous blockade of both K(+) channel types was necessary in WKY rats. Under basal conditions, the vasodilator action of both K(+) channels was enhanced in SHR compared to WKY rats. However, the overall contribution of K(+) channels to cAMP-induced vasodilator mechanisms is insufficient in genetic hypertension since a concurrent activation of both K(+) channels by cAMP overproduction is necessary for the prevention of BP rise elicited by acute NO/cGMP deficiency in SHR. This might be caused by less effective activation of these K(+) channels by cAMP in SHR. In conclusion, K(+) channels seem to have higher activity in SHR, but their vasodilator action cannot match sufficiently the augmented vasoconstriction in this hypertensive strain.

• MeSH
• agonisté adrenergních beta-receptorů MeSH
• AMP cyklický metabolismus   MeSH
• cévní rezistence MeSH
• draslíkové kanály řízené napětím metabolismus   MeSH
• hypertenze genetika   metabolismus   patofyziologie   MeSH
• isoprenalin MeSH
• krevní tlak MeSH
• NG-nitroargininmethylester MeSH
• potkani inbrední SHR MeSH
• potkani inbrední WKY MeSH
• synthasa oxidu dusnatého antagonisté a inhibitory   MeSH
• vápníkem aktivované draslíkové kanály s vysokou vodivostí - alfa-podjednotky metabolismus   MeSH
• vazodilatace * MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• agonisté adrenergních beta-receptorů MeSH
• AMP cyklický MeSH
• draslíkové kanály řízené napětím MeSH
• isoprenalin MeSH
• Kcnma1 protein, rat MeSH Prohlížeč
• NG-nitroargininmethylester MeSH
• synthasa oxidu dusnatého MeSH
• vápníkem aktivované draslíkové kanály s vysokou vodivostí - alfa-podjednotky MeSH