The aim of the present study was to assess systemic circulatory and tissue activities of both the classical arm and of the alternative arm of the renin-angiotensin system (RAS) in a new transgenic rat line (TG7371) that expresses angiotensin-(1-7) (ANG 1-7)-producing fusion protein; the results were compared with the activities measured in control transgene-negative Hannover Sprague-Dawley (HanSD) rats. Plasma and tissue concentrations of angiotensin II (ANG II) and ANG 1-7, and kidney mRNA expressions of receptors responsible for biological actions of ANG II and ANG 1-7 [i.e. ANG II type 1 and type 2 (AT1 and AT2) and Mas receptors] were assessed in TG7371 transgene-positive and in HanSD rats. We found that male TG7371 transgene-positive rats exhibited significantly elevated plasma, kidney, heart and lung ANG 1-7 concentrations as compared with control male HanSD rats; by contrast, there was no significant difference in ANG II concentrations and no significant differences in mRNA expression of AT1, AT2 and Mas receptors. In addition, we found that in male TG7371 transgene-positive rats blood pressure was lower than in male HanSD rats. These data indicate that the balance between the classical arm and the alternative arm of the RAS was in male TGR7371 transgene-positive rats markedly shifted in favor of the latter. In conclusion, TG7371 transgene-positive rats represent a new powerful tool to study the long-term role of the alternative arm of the RAS in the pathophysiology and potentially in the treatment of cardio-renal diseases.

• Klíčová slova
• Angiotensin II, Angiotensin-(1-7), Renin-angiotensin system, TG7371 transgenic rat,
• MeSH
• angiotensin I * metabolismus   MeSH
• angiotensin II * MeSH
• kardiovaskulární nemoci metabolismus   genetika   MeSH
• krevní tlak fyziologie   MeSH
• krysa rodu Rattus MeSH
• ledviny metabolismus   MeSH
• nemoci ledvin metabolismus   genetika   MeSH
• peptidové fragmenty * metabolismus   MeSH
• potkani Sprague-Dawley * MeSH
• potkani transgenní * MeSH
• protoonkogen Mas MeSH
• receptor angiotensinu typ 1 genetika   metabolismus   MeSH
• receptory spřažené s G-proteiny genetika   metabolismus   MeSH
• rekombinantní fúzní proteiny metabolismus   MeSH
• renin-angiotensin systém * fyziologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• angiotensin I (1-7) MeSH Prohlížeč
• angiotensin I * MeSH
• angiotensin II * MeSH
• peptidové fragmenty * MeSH
• protoonkogen Mas MeSH
• receptor angiotensinu typ 1 MeSH
• receptory spřažené s G-proteiny MeSH
• rekombinantní fúzní proteiny MeSH

Angiotensin-converting enzyme 2 (ACE2), one of the key enzymes of the renin-angiotensin system (RAS), plays an important role in SARS-CoV-2 infection by functioning as a virus receptor. Angiotensin peptides Ang I and Ang II, the substrates of ACE2, can modulate the binding of SARS-CoV-2 Spike protein to the ACE2 receptor. In the present work, we found that co incubation of HEK-ACE2 and Vero E6 cells with the SARS-CoV-2 Spike pseudovirus (PVP) resulted in stimulation of the virus entry at low and high micromolar concentrations of Ang I and Ang II, respectively. The potency of Ang I and Ang II stimulation of virus entry corresponds to their binding affinity to ACE2 catalytic pocket with 10 times higher efficiency of Ang II. The Ang II induced mild increase of PVP infectivity at 20 microM; while at 100 microM the increase (129.74+/-3.99 %) was highly significant (p<0.001). Since the angiotensin peptides act in HEK ACE2 cells without the involvement of angiotensin type I receptors, we hypothesize that there is a steric interaction between the catalytic pocket of the ACE2 enzyme and the SARS-CoV-2 S1 binding domain. Oversaturation of the ACE2 with their angiotensin substrate might result in increased binding and entry of the SARS-CoV-2. In addition, the analysis of angiotensin peptides metabolism showed decreased ACE2 and increased ACE activity upon SARS-CoV-2 action. These effects should be taken into consideration in COVID-19 patients suffering from comorbidities such as the over-activated renin-angiotensin system as a mechanism potentially influencing the SARS-CoV-2 invasion into recipient cells.

• MeSH
• angiotensin I metabolismus   farmakologie   MeSH
• angiotensin II metabolismus   MeSH
• angiotensin konvertující enzym metabolismus   MeSH
• angiotensin-konvertující enzym 2 metabolismus   MeSH
• COVID-19 * MeSH
• glykoprotein S, koronavirus * MeSH
• inhibitory ACE MeSH
• lidé MeSH
• renin-angiotensin systém * MeSH
• SARS-CoV-2 metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• angiotensin I MeSH
• angiotensin II MeSH
• angiotensin konvertující enzym MeSH
• angiotensin-konvertující enzym 2 MeSH
• glykoprotein S, koronavirus * MeSH
• inhibitory ACE MeSH
• spike protein, SARS-CoV-2 MeSH Prohlížeč

Abdominal aortic aneurysms (AAA) result from maladaptive remodeling of the vascular wall and reduces structural integrity. Angiotensin II (AngII) infusion has become a standard laboratory model for studying AAA initiation and progression. We determined the different vasoactive responses of various mouse arteries to Ang II. Ex vivo isometric tension analysis was conducted on 18-week-old male C57BL/6 mice (n = 4) brachiocephalic arteries (BC), iliac arteries (IL), and abdominal (AA) and thoracic aorta (TA). Arterial rings were mounted between organ hooks, gently stretched and an AngII dose response was performed. Rings were placed in 4% paraformaldehyde for immunohistochemistry analysis to quantify peptide expression of angiotensin type 1 (AT1R) and 2 receptors (AT2R) in the endothelium, media, and adventitia. Results from this study demonstrated vasoconstriction responses in IL were significantly higher at all AngII doses when compared to BC, and TA and AA responses (maximum constriction-IL: 68.64 ± 5.47% vs. BC: 1.96 ± 1.00%; TA: 3.13 ± 0.16% and AA: 2.75 ± 1.77%, p < 0.0001). Expression of AT1R was highest in the endothelium of IL (p < 0.05) and in the media and (p < 0.05) adventitia (p < 0.05) of AA. In contrast, AT2R expression was highest in endothelium (p < 0.05), media (p < 0.01, p < 0.05) and adventitia of TA. These results suggest that mouse arteries display different vasoactive responses to AngII, and the exaggerated response in IL arteries may play a role during AAA development.

• Klíčová slova
• Abdominal aortic aneurysm, Angiotensin II, Angiotensin type 1 receptor, Angiotensin type 2 receptor, Vasoconstriction,
• MeSH
• aneurysma břišní aorty * chemicky indukované   MeSH
• angiotensin I MeSH
• angiotensin II farmakologie   MeSH
• aortální aneurysma * MeSH
• arteria iliaca MeSH
• arterie MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• peptidové hormony * MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• angiotensin I MeSH
• angiotensin II MeSH
• peptidové hormony * MeSH

We used mass spectrometry to quantitate production of angiotensinogen metabolites in renal artery of 3- and 7-month-old Wistar-Kyoto (WKY) and Spontaneously Hypertensive Rats (SHR). Tissue fragments were incubated for 15 min in oxygenated buffer, with added angiotensin I. Concentrations of angiotensins I (ANG I), II (ANG II), III (ANG III), IV (ANG IV), angiotensin (1-9) [ANG (1-9)], angiotensin (1-7) [ANG (1-7)], and angiotensin (1-5) [ANG (1-5)], excreted into the buffer during experiment, were measured using liquid chromatography-mass spectrometry (LC/MS) and expressed per mg of dry tissue. Effects of pretreatment with 10 microM perindoprilat on the production of ANG I metabolites were quantitated. Background production of any of ANG I metabolites differed neither between WKY and SHR rats nor between 3- and 7-month-old rats. Perindoprilat pretreatment of renal arteries resulted, as expected, in decrease of ANG II production. However, renal arteries of 7-month-old SHR rats were resistant to ACE inhibitor and did not change ANG II production in response to perindoprilat. In renal arteries, taken from 3-month-old rats, pretreated with perindoprilat, incubation with ANG I, resulted in the level of ANG (1-9) significantly higher in SHR than WKY rats. Our conclusion is that in SHR rats, sensitivity of renal artery ACE to perindoprilat inhibition changes with age.

• MeSH
• angiotensin I metabolismus   MeSH
• arteria renalis účinky léků   metabolismus   MeSH
• hypertenze metabolismus   MeSH
• indoly farmakologie   MeSH
• peptidové fragmenty metabolismus   MeSH
• potkani inbrední SHR MeSH
• potkani inbrední WKY MeSH
• stárnutí metabolismus   MeSH
• techniky in vitro MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• angiotensin I (1-9) MeSH Prohlížeč
• angiotensin I MeSH
• indoly MeSH
• peptidové fragmenty MeSH
• perindoprilat MeSH Prohlížeč

OBJECTIVE: We evaluated the therapeutic effectiveness of a new, orally active epoxyeicosatrienoic acid analog (EET-A) in rats with angiotensin II (ANG II)-dependent malignant hypertension. METHODS: Malignant hypertension was induced in Cyp1a1-Ren-2 transgenic rats by activation of the renin gene using indole-3-carbinol (I3C), a natural xenobiotic. EET-A treatment was started either simultaneously with I3C induction process (early treatment) or 10 days later during established hypertension (late treatment). Blood pressure (BP) (radiotelemetry), indices of renal and cardiac injury, and plasma and kidney levels of the components of the renin-angiotensin system (RAS) were determined. RESULTS: In I3C-induced hypertensive rats, early EET-A treatment attenuated BP increase (to 175 ± 3 versus 193 ± 4 mmHg, P < 0.05, on day 13), reduced albuminuria (15 ± 1 versus 28 ± 2 mg/24 h, P < 0.05), and cardiac hypertrophy as compared with untreated I3C-induced rats. This was associated with suppression of plasma and kidney ANG II levels (48 ± 6 versus 106 ± 9 and 122 ± 19 versus 346 ± 11 fmol ml or g, respectively, P < 0.05) and increases in plasma and kidney angiotensin (1-7) concentrations (84 ± 9 versus 37 ± 6 and 199 ± 12 versus 68 ± 9 fmol/ml or g, respectively, P < 0.05). Remarkably, late EET-A treatment did not lower BP or improve renal and cardiac injury; indices of RAS activity were not affected. CONCLUSION: The new, orally active EET-A attenuated the development of experimental ANG II-dependent malignant hypertension, likely via suppression of the hypertensiogenic axis and augmentation of the vasodilatory/natriuretic axis of RAS.

• MeSH
• albuminurie farmakoterapie   MeSH
• angiotensin I metabolismus   MeSH
• angiotensin II metabolismus   MeSH
• časové faktory MeSH
• cytochrom P-450 CYP1A1 genetika   MeSH
• hypertenze maligní chemicky indukované   patofyziologie   prevence a kontrola   MeSH
• indoly MeSH
• krevní tlak účinky léků   MeSH
• krysa rodu Rattus MeSH
• kyselina 8,11,14-eikosatrienová analogy a deriváty   terapeutické užití   MeSH
• ledviny metabolismus   MeSH
• peptidové fragmenty metabolismus   MeSH
• potkani transgenní MeSH
• renin-angiotensin systém účinky léků   MeSH
• renin genetika   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• angiotensin I (1-7) MeSH Prohlížeč
• angiotensin I MeSH
• angiotensin II MeSH
• cytochrom P-450 CYP1A1 MeSH
• indole-3-carbinol MeSH Prohlížeč
• indoly MeSH
• kyselina 8,11,14-eikosatrienová MeSH
• peptidové fragmenty MeSH
• Ren2 protein, rat MeSH Prohlížeč
• renin MeSH

The role of the intrarenal renin-angiotensin system (RAS) in the pathophysiology of malignant hypertension is not fully understood. Accumulating evidence indicates that the recently discovered vasodilator axis of the RAS, angiotensin-converting enzyme (ACE) type 2 (ACE2)/angiotensin 1-7 (ANG 1-7), constitutes an endogenous system counterbalancing the hypertensiogenic axis, ACE/angiotensin II (ANG II)/AT1 receptor. This study aimed to evaluate the role of the intrarenal vasodilator RAS axis in the pathophysiology of ANG II-dependent malignant hypertension in Cyp1a1-Ren-2 transgenic rats. ANG II-dependent malignant hypertension was induced by 13 days' dietary administration of indole-3-carbinol (I3C), a natural xenobiotic that activates the mouse renin gene in Cyp1a1-Ren-2 transgenic rats. It was hypothesized that pharmacologically-induced inhibition of the ACE2/ANG 1-7 complex should aggravate, and activation of this axis should attenuate, the course of ANG II-dependent malignant hypertension. Blood pressure (BP) was monitored by radiotelemetry. ACE2 inhibitor (DX 600, 0.2 μg/day) and ACE2 activator (DIZE, 1 mg/day) were administrated via osmotic minipumps. Even though ACE2 inhibitor significantly decreased and ACE2 activator increased intrarenal ANG 1-7 concentrations, the course of BP, as well as of albuminuria, cardiac hypertrophy and renal glomerular damage, were not altered. It was shown that intrarenal alterations in the ACE2/ANG 1-7 complex did not significantly modify the course of malignant hypertension in I3C-induced Cyp1a1-Ren-2 transgenic rats. Thus, in our experimental setting alterations of this intrarenal vasodilator complex of the RAS do not significantly modify the form of malignant hypertension that clearly depends on the inappropriately increased activity of the ACE/ANG II/AT1 receptor axis.

• Klíčová slova
• angiotensin 1-7, angiotensin II, angiotensin-converting enzyme type 2, malignant hypertension, renin-angiotensin system,
• MeSH
• aktivátory enzymů farmakologie   MeSH
• albuminurie komplikace   MeSH
• angiotensin I metabolismus   MeSH
• angiotensin konvertující enzym metabolismus   MeSH
• angiotensin-konvertující enzym 2 MeSH
• cytochrom P-450 CYP1A1 genetika   MeSH
• diminazen analogy a deriváty   farmakologie   MeSH
• hypertenze maligní komplikace   metabolismus   patofyziologie   moč   MeSH
• krevní tlak účinky léků   MeSH
• krysa rodu Rattus MeSH
• ledviny účinky léků   metabolismus   MeSH
• myši MeSH
• peptidové fragmenty metabolismus   MeSH
• peptidy farmakologie   MeSH
• potkani transgenní MeSH
• regulace genové exprese účinky léků   MeSH
• renin-angiotensin systém účinky léků   MeSH
• renin genetika   MeSH
• sodík moč   MeSH
• tělesná hmotnost účinky léků   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• Ace2 protein, mouse MeSH Prohlížeč
• Ace2 protein, rat MeSH Prohlížeč
• aktivátory enzymů MeSH
• angiotensin I (1-7) MeSH Prohlížeč
• angiotensin I MeSH
• angiotensin konvertující enzym MeSH
• angiotensin-konvertující enzym 2 MeSH
• cytochrom P-450 CYP1A1 MeSH
• diminazen MeSH
• diminazene aceturate MeSH Prohlížeč
• DX600 peptide MeSH Prohlížeč
• peptidové fragmenty MeSH
• peptidy MeSH
• Ren2 protein, mouse MeSH Prohlížeč
• renin MeSH
• sodík MeSH

The present study was performed to evaluate the role of intrapulmonary activity of the two axes of the renin-angiotensin system (RAS): vasoconstrictor angiotensin-converting enzyme (ACE)/angiotensin II (ANG II)/ANG II type 1 receptor (AT₁) axis, and vasodilator ACE type 2 (ACE2)/angiotensin 1-7 (ANG 1-7)/Mas receptor axis, in the development of hypoxic pulmonary hypertension in Ren-2 transgenic rats (TGR). Transgene-negative Hannover Sprague-Dawley (HanSD) rats served as controls. Both TGR and HanSD rats responded to two weeks´ exposure to hypoxia with a significant increase in mean pulmonary arterial pressure (MPAP), however, the increase was much less pronounced in the former. The attenuation of hypoxic pulmonary hypertension in TGR as compared to HanSD rats was associated with inhibition of ACE gene expression and activity, inhibition of AT₁receptor gene expression and suppression of ANG II levels in lung tissue. Simultaneously, there was an increase in lung ACE2 gene expression and activity and, in particular, ANG 1-7 concentrations and Mas receptor gene expression. We propose that a combination of suppression of ACE/ANG II/AT₁receptor axis and activation of ACE2/ANG 1-7/Mas receptor axis of the RAS in the lung tissue is the main mechanism explaining attenuation of hypoxic pulmonary hypertension in TGR as compared with HanSD rats.

• MeSH
• angiotensin I metabolismus   MeSH
• angiotensin II metabolismus   MeSH
• angiotensin konvertující enzym metabolismus   MeSH
• angiotensin-konvertující enzym 2 MeSH
• arteriální tlak MeSH
• hypoxie komplikace   enzymologie   patofyziologie   MeSH
• modely nemocí na zvířatech MeSH
• peptidové fragmenty metabolismus   MeSH
• plíce enzymologie   MeSH
• plicní hypertenze enzymologie   genetika   patofyziologie   prevence a kontrola   MeSH
• potkani Sprague-Dawley MeSH
• potkani transgenní MeSH
• protoonkogen Mas MeSH
• protoonkogenní proteiny metabolismus   MeSH
• receptor angiotensinu typ 1 metabolismus   MeSH
• receptory spřažené s G-proteiny metabolismus   MeSH
• renin-angiotensin systém * MeSH
• renin genetika   metabolismus   MeSH
• signální transdukce MeSH
• vazodilatace MeSH
• vazokonstrikce MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• Ace2 protein, mouse MeSH Prohlížeč
• Ace2 protein, rat MeSH Prohlížeč
• angiotensin I (1-7) MeSH Prohlížeč
• angiotensin I MeSH
• angiotensin II MeSH
• angiotensin konvertující enzym MeSH
• angiotensin-konvertující enzym 2 MeSH
• peptidové fragmenty MeSH
• protoonkogen Mas MeSH
• protoonkogenní proteiny MeSH
• receptor angiotensinu typ 1 MeSH
• receptory spřažené s G-proteiny MeSH
• Ren2 protein, mouse MeSH Prohlížeč
• renin MeSH

The aim of the present study was to test the hypothesis that chronic hypoxia would aggravate hypertension in Ren-2 transgenic rats (TGR), a well-defined monogenetic model of hypertension with increased activity of endogenous renin-angiotensin system (RAS). Systolic blood pressure (SBP) in conscious rats and mean arterial pressure (MAP) in anesthetized TGR and normotensive Hannover Sprague-Dawley (HanSD) rats were determined under normoxia that was either continuous or interrupted by two weeks´ hypoxia. Expression, activities and concentrations of individual components of RAS were studied in plasma and kidney of TGR and HanSD rats under normoxic conditions and after exposure to chronic hypoxia. In HanSD rats two weeks´ exposure to chronic hypoxia did not alter SBP and MAP. Surprisingly, in TGR it decreased markedly SBP and MAP; this was associated with substantial reduction in plasma and kidney renin activities and also of angiotensin II (ANG II) levels, without altering angiotensin-converting enzyme (ACE) activities. Simultaneously, in TGR the exposure to hypoxia increased kidney ACE type 2 (ACE2) activity and angiotensin 1-7 (ANG 1-7) concentrations as compared with TGR under continuous normoxia. Based on these results, we propose that suppression of the hypertensiogenic ACE-ANG II axis in the circulation and kidney tissue, combined with augmentation of the intrarenal vasodilator ACE2-ANG 1-7 axis, is the main mechanism responsible for the blood pressure-lowering effects of chronic hypoxia in TGR.

• MeSH
• angiotensin I krev   MeSH
• angiotensin II krev   MeSH
• angiotensin konvertující enzym krev   MeSH
• angiotensin-konvertující enzym 2 MeSH
• hypertenze krev   genetika   patofyziologie   prevence a kontrola   MeSH
• hypoxie komplikace   enzymologie   patofyziologie   MeSH
• krevní tlak MeSH
• ledviny enzymologie   MeSH
• modely nemocí na zvířatech MeSH
• peptidové fragmenty krev   MeSH
• potkani Sprague-Dawley MeSH
• potkani transgenní MeSH
• protoonkogen Mas MeSH
• protoonkogenní proteiny krev   MeSH
• receptory spřažené s G-proteiny krev   MeSH
• renin-angiotensin systém * MeSH
• renin krev   genetika   MeSH
• signální transdukce MeSH
• vazodilatace * MeSH
• vazokonstrikce * MeSH
• věkové faktory MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• Ace2 protein, mouse MeSH Prohlížeč
• Ace2 protein, rat MeSH Prohlížeč
• angiotensin I (1-7) MeSH Prohlížeč
• angiotensin I MeSH
• angiotensin II MeSH
• angiotensin konvertující enzym MeSH
• angiotensin-konvertující enzym 2 MeSH
• peptidové fragmenty MeSH
• protoonkogen Mas MeSH
• protoonkogenní proteiny MeSH
• receptory spřažené s G-proteiny MeSH
• Ren2 protein, mouse MeSH Prohlížeč
• renin MeSH

The detailed mechanisms determining the course of congestive heart failure (CHF) in hypertensive subjects with associated renal dysfunction remain unclear. In Ren-2 transgenic rats (TGR), a model of angiotensin II (ANG II)-dependent hypertension, CHF was induced by volume overload achieved by creation of the aorto-caval fistula (ACF). In these rats we investigated the putative pathophysiological contribution of epoxyeicosatrienoic acids (EETs) and compared it with the role of the renin-angiotensin system (RAS). We found that untreated ACF TGR exhibited marked intrarenal and myocardial deficiency of EETs and impairment of renal function. Chronic treatment of these rats with cis-4-[4-(3-adamantan-1-yl-ureido)cyclohexyloxy]benzoic acid (c-AUCB, 3 mg/L in drinking water), an inhibitor of soluble epoxide hydrolase (sEH) which normally degrades EETs, increased intrarenal and myocardial EETs, markedly improved survival rate, and increased renal blood flow, glomerular filtration rate and fractional sodium excretion, without altering RAS activity. Chronic angiotensin-converting enzyme inhibition (ACEi) with trandolapril, (6 mg/L in drinking water) improved survival rate even more, and also inhibited the development of renal dysfunction; these beneficial actions were associated with significant suppression of the vasoconstrictor/sodium retaining axis and further activation of the vasodilatory/natriuretic axis of the systemic and intrarenal RAS, without modifying tissue availability of biologically active fatty acid epoxides. In conclusion, these findings strongly suggest that chronic sEH inhibition and chronic treatment with ACEi, each of them altering a different vasoactive system, delay or even prevent the onset of decompensation of CHF in ACF TGR, probably by preventing the development of renal dysfunction.

• Klíčová slova
• aorto-caval fistula, congestive heart failure, epoxyeicosatrienoic acids, hypertension, renal dysfunction, renin-angiotensin system, soluble epoxide hydrolase,
• MeSH
• angiotensin I metabolismus   MeSH
• angiotensin II metabolismus   MeSH
• aorta MeSH
• časové faktory MeSH
• epoxid hydrolasy antagonisté a inhibitory   chemie   MeSH
• hemodynamika účinky léků   MeSH
• inhibitory ACE farmakologie   terapeutické užití   MeSH
• inhibitory enzymů farmakologie   terapeutické užití   MeSH
• krevní tlak účinky léků   MeSH
• krysa rodu Rattus MeSH
• kyseliny mastné mononenasycené metabolismus   MeSH
• ledviny účinky léků   patofyziologie   MeSH
• peptidové fragmenty metabolismus   MeSH
• píštěle komplikace   MeSH
• potkani transgenní MeSH
• progrese nemoci * MeSH
• renin-angiotensin systém účinky léků   MeSH
• renin genetika   MeSH
• rozpustnost MeSH
• srdeční frekvence účinky léků   MeSH
• srdeční selhání farmakoterapie   etiologie   patofyziologie   MeSH
• systém (enzymů) cytochromů P-450 metabolismus   MeSH
• vena cava inferior MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• angiotensin I (1-7) MeSH Prohlížeč
• angiotensin I MeSH
• angiotensin II MeSH
• eicosenoic acid MeSH Prohlížeč
• epoxid hydrolasy MeSH
• inhibitory ACE MeSH
• inhibitory enzymů MeSH
• kyseliny mastné mononenasycené MeSH
• peptidové fragmenty MeSH
• renin MeSH
• systém (enzymů) cytochromů P-450 MeSH

The detailed mechanisms determining the course of congestive heart failure (CHF) and associated renal dysfunction remain unclear. In a volume overload model of CHF induced by creation of aorto-caval fistula (ACF) in Hannover Sprague-Dawley (HanSD) rats we explored the putative pathogenetic contribution of epoxyeicosatrienoic acids (EETs), active products of CYP-450 dependent epoxygenase pathway of arachidonic acid metabolism, and compared it with the role of the renin-angiotensin system (RAS). Chronic treatment with cis-4-[4-(3-adamantan-1-yl-ureido) cyclohexyloxy]benzoic acid (c-AUCB, 3 mg/l in drinking water), an inhibitor of soluble epoxide hydrolase (sEH) which normally degrades EETs, increased intrarenal and myocardial EETs to levels observed in sham-operated HanSD rats, but did not improve the survival or renal function impairment. In contrast, chronic angiotensin-converting enzyme inhibition (ACEi, trandolapril, 6 mg/l in drinking water) increased renal blood flow, fractional sodium excretion and markedly improved survival, without affecting left ventricular structure and performance. Hence, renal dysfunction rather than cardiac remodeling determines long-term mortality in advanced stage of CHF due to volume overload. Strong protective actions of ACEi were associated with suppression of the vasoconstrictor/sodium retaining axis and activation of vasodilatory/natriuretic axis of the renin-angiotensin system in the circulating blood and kidney tissue.

• MeSH
• angiotensin I krev   MeSH
• angiotensin II krev   MeSH
• benzoáty farmakologie   terapeutické užití   MeSH
• epoxid hydrolasy antagonisté a inhibitory   MeSH
• epoxidové sloučeniny metabolismus   MeSH
• inhibitory ACE MeSH
• krysa rodu Rattus MeSH
• kyselina 8,11,14-eikosatrienová analogy a deriváty   krev   metabolismus   MeSH
• ledviny metabolismus   MeSH
• močovina analogy a deriváty   farmakologie   terapeutické užití   MeSH
• modely nemocí na zvířatech MeSH
• myokard metabolismus   MeSH
• náhodné rozdělení MeSH
• peptidové fragmenty krev   MeSH
• preklinické hodnocení léčiv MeSH
• renální insuficience krev   etiologie   prevence a kontrola   MeSH
• renin-angiotensin systém účinky léků   MeSH
• srdeční selhání krev   komplikace   diagnostické zobrazování   farmakoterapie   MeSH
• ultrasonografie MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• 4-(4-(3-adamantan-1-ylureido)cyclohexyloxy)benzoic acid MeSH Prohlížeč
• angiotensin I (1-7) MeSH Prohlížeč
• angiotensin I MeSH
• angiotensin II MeSH
• benzoáty MeSH
• epoxid hydrolasy MeSH
• epoxidové sloučeniny MeSH
• inhibitory ACE MeSH
• kyselina 8,11,14-eikosatrienová MeSH
• močovina MeSH
• peptidové fragmenty MeSH