scholarly journals Altered Renal Vascular Responsiveness to Vasoactive Agents in Rats with Angiotensin II-Dependent Hypertension and Congestive Heart Failure

2019 ◽  
Vol 44 (4) ◽  
pp. 792-809 ◽  
Author(s):  
Šárka Vacková ◽  
Soňa Kikerlová ◽  
Vojtěch Melenovsky ◽  
František Kolář ◽  
John D. Imig ◽  
...  
Keyword(s):  
Heart Failure ◽  
Congestive Heart Failure ◽  
Angiotensin Ii ◽  
Renal Dysfunction ◽  
Volume Overload ◽  
Epoxyeicosatrienoic Acids ◽  
Ang Ii ◽  
Vasoactive Agents ◽  
Vascular Responsiveness ◽  
Renal Vascular

Objective: We evaluated the hypothesis that the development of renal dysfunction and congestive heart failure (CHF) caused by volume overload in rats with angiotensin II (ANG II)-dependent hypertension is associated with altered renal vascular responsiveness to ANG II and to epoxyeicosatrienoic acids (EETs). Methods: Ren-2 transgenic rats (TGRs) were used as a model of ANG II-dependent hypertension. CHF was induced by volume overload achieved by the creation of the aorto-caval fistula (ACF). Renal blood flow (RBF) responses were determined to renal arterial administration of ANG II, native 11,12-EET, an analog of 14,15-EETs (EET-A), norepinephrine (NE), acetylcholine (Ach) and bradykinin (Bk) in healthy (i.e., sham-operated) TGR and ACF TGR (5 weeks after ACF creation). Results: Selective intrarenal administration of neither vasoactive drug altered mean arterial pressure in any group. Administration of ANG II caused greater decreases in RBF in ACF TGR than in sham-operated TGR, whereas after administration of NE the respective decreases were comparable in the 2 groups. Administration of Ach and Bk elicited significantly higher RBF increases in ACF TGR as compared with sham-operated TGR. In contrast, administration of 11,12-EET and EET-A caused significantly smaller RBF increases in ACF TGR than in sham-operated TGR. Conclusion: The findings show that 5 weeks after creation of ACF, the TGR exhibit exaggerated renal vasoconstrictor responses to ANG II and reduced renal vasodilatory responses to EETs, suggesting that both these alterations might play an important role in the development of renal dysfunction in this model of CHF.

scholarly journals Enhanced Renal Vascular Responsiveness to Angiotensin II and Norepinephrine: A Unique Feature of Female Rats with Congestive Heart Failure

2019 ◽  
Vol 44 (5) ◽  
pp. 1128-1141 ◽  
Author(s):  
Vojtěch Krátký ◽  
Soňa Kikerlová ◽  
Zuzana Husková ◽  
Janusz Sadowski ◽  
František Kolář ◽  
...  
Keyword(s):  
Heart Failure ◽  
Angiotensin Ii ◽  
Renal Dysfunction ◽  
Unique Feature ◽  
Female Rats ◽  
Male Rats ◽  
Published Data ◽  
Ang Ii ◽  
Vascular Responsiveness ◽  
Renal Vascular

Background/Aims: We found recently that the aortocaval fistula (ACF)-induced heart failure (HF) results in higher mortality in female than in male rats. Possibly, the development of renal dysfunction in the females, unlike in males, is associated with altered renal vascular responsiveness to angiotensin II (ANG II). Methods: Five or 20 weeks after ACF creation (compensated and decompensated HF, respectively), we assessed renal blood flow (RBF) responses to intrarenal administration of ANG II, norepinephrine (NE), and acetylcholine (Ach) in female ACF and sham-operated rats. Results: In ACF females, ANG II decreased RBF more than in healthy animals, unlike with earlier published data in male ACF rats that responded similarly. Also, NE decreased RBF more in female ACF rats, whereas Ach increased RBF to the same extent in female ACF and sham-operated rats. RBF responses to intravenous administration of NE and Ach were almost identical in female and male ACF rats. Conclusion: Female ACF rats studied at the onset of HF decompensation reveal, in contrast to male rats, enhanced renal vascular responsiveness to both NE and ANG II. When associated with the demonstrated increased intrarenal ANG II and NE concentrations, such hyperresponsiveness might promote the development of renal dysfunction and accelerate HF decompensation.

scholarly journals Effects of Renal Denervation on the Enhanced Renal Vascular Responsiveness to Angiotensin II in High-Output Heart Failure: Angiotensin II Receptor Binding Assessment and Functional Studies in Ren-2 Transgenic Hypertensive Rats

Biomedicines ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 1803
Author(s):  
Zuzana Honetschlägerová ◽  
Lucie Hejnová ◽  
Jiří Novotný ◽  
Aleš Marek ◽  
Luděk Červenka
Keyword(s):  
Heart Failure ◽  
Angiotensin Ii ◽  
Receptor Binding ◽  
Renal Denervation ◽  
Kidney Cortex ◽  
Ang Ii ◽  
Angiotensin Ii Receptor ◽  
Vascular Responsiveness ◽  
Renal Vascular ◽  
High Output

Detailed mechanism(s) of the beneficial effects of renal denervation (RDN) on the course of heart failure (HF) remain unclear. The study aimed to evaluate renal vascular responsiveness to angiotensin II (ANG II) and to characterize ANG II type 1 (AT1) and type 2 (AT2) receptors in the kidney of Ren-2 transgenic rats (TGR), a model of ANG II-dependent hypertension. HF was induced by volume overload using aorto-caval fistula (ACF). The studies were performed two weeks after RDN (three weeks after the creation of ACF), i.e., when non-denervated ACF TGR enter the decompensation phase of HF whereas those after RDN are still in the compensation phase. We found that ACF TGR showed lower renal blood flow (RBF) and its exaggerated response to intrarenal ANG II (8 ng); RDN further augmented this responsiveness. We found that all ANG II receptors in the kidney cortex were of the AT1 subtype. ANG II receptor binding characteristics in the renal cortex did not significantly differ between experimental groups, hence AT1 alterations are not responsible for renal vascular hyperresponsiveness to ANG II in ACF TGR, denervated or not. In conclusion, maintained renal AT1 receptor binding combined with elevated ANG II levels and renal vascular hyperresponsiveness to ANG II in ACF TGR influence renal hemodynamics and tubular reabsorption and lead to renal dysfunction in the high-output HF model. Since RDN did not attenuate the RBF decrease and enhanced renal vascular responsiveness to ANG II, the beneficial actions of RDN on HF-related mortality are probably not dominantly mediated by renal mechanism(s).

scholarly journals Renal Sympathetic Denervation Attenuates Congestive Heart Failure in Angiotensin II-Dependent Hypertension: Studies with Ren-2 Transgenic Hypertensive Rats with Aortocaval Fistula

2021 ◽  
pp. 1-19
Author(s):  
Zuzana Honetschlagerová ◽  
Olga Gawrys ◽  
Šárka Jíchová ◽  
Petra Škaroupková ◽  
Soňa Kikerlová ◽  
...  
Keyword(s):  
Heart Failure ◽  
Survival Rate ◽  
Angiotensin Ii ◽  
Renal Sympathetic Denervation ◽  
Aortocaval Fistula ◽  
Ang Ii ◽  
Vascular Responsiveness ◽  
Final Survival ◽  
Renal Vascular ◽  
Renal Sympathetic

<b><i>Objective:</i></b> We examined if renal denervation (RDN) attenuates the progression of aortocaval fistula (ACF)-induced heart failure or improves renal hemodynamics in Ren-2 transgenic rats (TGR), a model of angiotensin II (ANG II)-dependent hypertension. <b><i>Methods:</i></b> Bilateral RDN was performed 1 week after creation of ACF. The animals studied were ACF TGR and sham-operated controls, and both groups were subjected to RDN or sham denervation. In separate groups, renal artery blood flow (RBF) responses were determined to intrarenal ANG II (2 and 8 ng), norepinephrine (NE) (20 and 40 ng) and acetylcholine (Ach) (10 and 40 ng) 3 weeks after ACF creation. <b><i>Results:</i></b> In nondenervated ACF TGR, the final survival rate was 10 versus 50% in RDN rats. RBF was significantly lower in ACF TGR than in sham-operated TGR (6.2 ± 0.3 vs. 9.7 ± 0.5 mL min<sup>−1</sup> g<sup>−1</sup>, <i>p</i> &#x3c; 0.05), the levels unaffected by RDN. Both doses of ANG II decreased RBF more in ACF TGR than in sham-operated TGR (−19 ± 3 vs. −9 ± 2% and −47 ± 3 vs. −22 ± 2%, <i>p</i> &#x3c; 0.05 in both cases). RDN did not alter RBF responses to the lower dose, but increased it to the higher dose of ANG II in sham-operated as well as in ACF TGR. NE comparably decreased RBF in ACF TGR and sham-operated TGR, and RDN increased RBF responsiveness. Intrarenal Ach increased RBF significantly more in ACF TGR than in sham-operated TGR (29 ± 3 vs. 17 ± 3%, <i>p</i> &#x3c; 0.05), the changes unaffected by RDN. ACF creation induced marked bilateral cardiac hypertrophy and lung congestion, both attenuated by RDN. In sham-operated but not in ACF TGR, RDN significantly decreased mean arterial pressure. <b><i>Conclusion:</i></b> The results show that RDN significantly improved survival rate in ACF TGR; however, this beneficial effect was not associated with improvement of reduced RBF or with attenuation of exaggerated renal vascular responsiveness to ANG II.

EFFECTS OF LONG-TERM EXTRARENAL ANGIOTENSIN II INFUSION ON RENAL VASCULAR RESPONSIVENESS TO VASOACTIVE AGENTS

1998 ◽  
Vol 25 (7-8) ◽  
pp. 633-636
Author(s):  
Sharyn M. Fitzgerald ◽  
Kathleen M. Stevenson ◽  
Roger G. Evans ◽  
Warwick P. Anderson
Keyword(s):  
Angiotensin Ii ◽  
Vasoactive Agents ◽  
Vascular Responsiveness ◽  
Renal Vascular

scholarly journals The Role of Renal Vascular Reactivity in the Development of Renal Dysfunction in Compensated and Decompensated Congestive Heart Failure

2018 ◽  
Vol 43 (6) ◽  
pp. 1730-1741 ◽  
Author(s):  
Vojtech Kratky ◽  
Libor Kopkan ◽  
Sona Kikerlova ◽  
Zuzana Huskova ◽  
Milos Taborsky ◽  
...  
Keyword(s):  
Heart Failure ◽  
Congestive Heart Failure ◽  
Renal Dysfunction ◽  
Vascular Reactivity ◽  
Renal Vascular

Angiotensin II-Vasopressin Interactions in The Regulation of Cardiovascular Functions. Evidence for an Impaired Hormonal Sympathetic Reflex in Hypertension and Congestive Heart Failure

2021 ◽  
Vol 21 ◽  
Author(s):  
Michele Iovino ◽  
Giuseppe Lisco ◽  
Vito Angelo Giagulli ◽  
Aldo Vanacore ◽  
Alberto Pesce ◽  
...  
Keyword(s):  
Heart Failure ◽  
Congestive Heart Failure ◽  
Angiotensin Ii ◽  
Cardiovascular Diseases ◽  
Electrolyte Balance ◽  
Ang Ii ◽  
Hormonal Imbalance ◽  
Impaired Water ◽  
Cardiovascular Functions

Conclusion: Hormonal imbalance between ANG II, VP, and SNS may induce hypertension and impaired water-electrolyte balance in cardiovascular diseases.

scholarly journals Angiotensin II Reduces Food Intake by Altering Orexigenic Neuropeptide Expression in the Mouse Hypothalamus

Endocrinology ◽  
2012 ◽  
Vol 153 (3) ◽  
pp. 1411-1420 ◽  
Author(s):  
Tadashi Yoshida ◽  
Laura Semprun-Prieto ◽  
Richard D. Wainford ◽  
Sergiy Sukhanov ◽  
Daniel R. Kapusta ◽  
...  
Keyword(s):  
Heart Failure ◽  
Congestive Heart Failure ◽  
Chronic Disease ◽  
Angiotensin Ii ◽  
Food Intake ◽  
End Stage Renal Disease ◽  
Ang Ii ◽  
Disease States ◽  
Stage Renal Disease ◽  
End Stage

Angiotensin II (Ang II), which is elevated in many chronic disease states such as end-stage renal disease and congestive heart failure, induces cachexia and skeletal muscle wasting by increasing muscle protein breakdown and reducing food intake. Neurohormonal mechanisms that mediate Ang II-induced appetite suppression are unknown. Consequently, we examined the effect of Ang II on expression of genes regulating appetite. Systemic Ang II (1 μg/kg · min) infusion in FVB mice rapidly reduced hypothalamic expression of neuropeptide Y (Npy) and orexin and decreased food intake at 6 h compared with sham-infused controls but did not change peripheral leptin, ghrelin, adiponectin, glucagon-like peptide, peptide YY, or cholecystokinin levels. These effects were completely blocked by the Ang II type I receptor antagonist candesartan or deletion of Ang II type 1a receptor. Ang II markedly reduced phosphorylation of AMP-activated protein kinase (AMPK), an enzyme that is known to regulate Npy expression. Intracerebroventricular Ang II infusion (50 ng/kg · min) caused a reduction of food intake, and Ang II dose dependently reduced Npy and orexin expression in the hypothalamus cultured ex vivo. The reduction of Npy and orexin in hypothalamic cultures was completely prevented by candesartan or the AMPK activator 5-aminoimidazole-4-carboxamide ribonucleoside. Thus, Ang II type 1a receptor-dependent Ang II signaling reduces food intake by suppressing the hypothalamic expression of Npy and orexin, likely via AMPK dephosphorylation. These findings have major implications for understanding mechanisms of cachexia in chronic disease states such as congestive heart failure and end-stage renal disease, in which the renin-angiotensin system is activated.

scholarly journals Inhibition of Soluble Epoxide Hydrolase Does Not Improve the Course of Congestive Heart Failure and the Development of Renal Dysfunction in Rats With Volume Overload Induced by Aorto-Caval Fistula

2015 ◽  
pp. 857-873 ◽  
Author(s):  
L. ČERVENKA ◽  
V. MELENOVSKÝ ◽  
Z. HUSKOVÁ ◽  
A. SPORKOVÁ ◽  
M. BÜRGELOVÁ ◽  
...  
Keyword(s):  
Heart Failure ◽  
Congestive Heart Failure ◽  
Drinking Water ◽  
Renal Dysfunction ◽  
Epoxide Hydrolase ◽  
Renin Angiotensin System ◽  
Volume Overload ◽  
Soluble Epoxide Hydrolase ◽  
Angiotensin System ◽  
Renin Angiotensin

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.

scholarly journals Regulation of L-type inward calcium channel activity by captopril and angiotensin II via the phosphatidyl inositol 3-kinase pathway in cardiomyocytes from volume-overload hypertrophied rat hearts

2011 ◽  
Vol 89 (3) ◽  
pp. 206-215 ◽  
Author(s):  
Zikiar Alvin ◽  
Graham G. Laurence ◽  
Bernell R Coleman ◽  
Aiqiu Zhao ◽  
Majd Hajj-Moussa ◽  
...  
Keyword(s):  
Heart Failure ◽  
Angiotensin Ii ◽  
Cardiac Hypertrophy ◽  
Phosphatidyl Inositol ◽  
Volume Overload ◽  
Acute Administration ◽  
Dependent Manner ◽  
Ang Ii ◽  
Patch Clamp Technique ◽  
Humoral Factors

Heart failure can be caused by pro-hypertrophic humoral factors such as angiotensin II (Ang II), which regulates protein kinase activities. The intermingled responses of these kinases lead to the early compensated cardiac hypertrophy, but later to the uncompensated phase of heart failure. We have shown that although beneficial, cardiac hypertrophy is associated with modifications in ion channels that are mainly mediated through mitogen-activated protein (MAP) kinase and phosphatidylinositol 3-kinase (PI3K) activation. This study evaluates the control of L-type Ca2+ current (ICa,L) by the Ang II/PI3K pathway in hypertrophied ventricular myocytes from volume-overload rats using the perforated patch-clamp technique. To assess activation of the ICa,L in cardiomyocytes, voltages of 350 ms in 10 mV increments from a holding potential of –85 mV were applied to cardiocytes, with a pre-pulse to –45 mV for 300 ms. Volume overload-induced hypertrophy reduces ICa,L, whereas addition of Ang II alleviates the hypertrophic-induced decrease in a PI3K-dependent manner. Acute administration of Ang II (10−6 mol/L) to normal adult cardiomyocytes had no effect; however, captopril reduced their basal ICa,L. In parallel, captopril regressed the hypertrophy and inverted the Ang II effect on ICa,L seemingly through a PI3K upstream effector. Thus, it seems that regression of cardiac hypertrophy by captopril improved ICa,L partly through PI3K.

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