Effects of renal sympathetic denervation on the course of congestive heart failure combined with chronic kidney disease: Insight from studies with fawn-hooded hypertensive rats with volume overload induced using aorto-caval fistula

Honetschlägerová, Zuzana; Škaroupková, Petra; Kikerlová, Soňa; Husková, Zuzana; Maxová, Hana; Melenovský, Vojtěch; Kompanowska-Jezierska, Elżbieta; Sadowski, Janusz; Gawryś, Olga; Kujal, Petr; Červenka, Luděk; Chábová, Věra Čertíková

doi:10.1080/10641963.2021.1907398

Cited by 10 publications

(29 citation statements)

References 77 publications

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“…In this model of high-output HF, the induction of ACF resulted in a progressive rise in albuminuria. In addition, the gradual increase in albumin excretion after the induction of ACF was also found in the control strain, i.e., in Fawn-hooded low-pressure rats (FHL), that do not spontaneously develop CKD [32]. Our working hypothesis is that the decrease in albuminuria in TGR in response to ACF could be mediated by more pronounced initial renal hypoperfusion in ACF TGR as compared with ACF FHH.…”

Section: Series 3: Effects Of Single Treatment With Eet-a or Acei Or With A Combination Thereof On The Survival Rate And Albuminuriamentioning

confidence: 75%

“…Chronic HF due to volume overload was induced by creating ACF using a needle technique. This procedure is routinely performed in our laboratory, and the technique's details were reported previously [26,31,32,37,51]. Shamoperated rats underwent an identical procedure but without creating the ACF.…”

Section: Heart Failure Model Exclusion Criteriamentioning

confidence: 99%

“…In addition, Western blot analysis of protein expression of CYP4A1, CYP2C23, and CYP2J3 in the kidney cortex and LV tissue was performed. These methods are described in detail in our previous studies and are routinely employed in our laboratory [31,32,[36][37][38][39][40]53,56,57]. Male rats of the same age as in series 1 and 2 derived from numerous litters were randomly assigned to experimental procedures (sham-operation or ACF creation).…”

Section: Acf Tgrmentioning

confidence: 99%

“…The follow-up period was until day +140 (20 weeks). On the days labeled 0, +14, +28, +70, and +140, the animals were placed in metabolic cages, and 24-h urinary albuminuria was assessed as described previously [32]. To obtain reliable data regarding the effects of treatment regimens on the survival rate and to have a sufficient number of rats to analyze cardiac function and structure by echocardiography and LV pressure-volume analysis, relatively high initial n values were used (also in sham-operated animals).…”

Section: Acf Tgrmentioning

confidence: 99%

“…ACF presents a well-defined model of heart failure due to volume overload, characterized by activation of the RAS, congestion, and impairment of renal function. The model has many features in common with untreated human HF [26][27][28][29][30][31][32] and is recommended by the American Heart Association and the European Society of Cardiology for preclinical testing to identify new targets for the treatment of HF patients [33,34]. The TGR model combines activation of the RAS and hypertension [35,36], two well-recognized critical factors for the progression of HF [1,2,6,12,13,16].…”

Section: Introductionmentioning

confidence: 99%

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Effects of Epoxyeicosatrienoic Acid-Enhancing Therapy on the Course of Congestive Heart Failure in Angiotensin II-Dependent Rat Hypertension: From mRNA Analysis towards Functional In Vivo Evaluation

et al. 2021

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This study evaluates the effects of chronic treatment with EET-A, an orally active epoxyeicosatrienoic acid (EETs) analog, on the course of aorto-caval fistula (ACF)-induced heart failure (HF) in Ren-2 transgenic rats (TGR), a model characterized by hypertension and augmented activity of the renin-angiotensin system (RAS). The results were compared with standard pharmacological blockade of the RAS using angiotensin-converting enzyme inhibitor (ACEi). The rationale for employing EET-A as a new treatment approach is based on our findings that apart from increased RAS activity, untreated ACF TGR also shows kidney and left ventricle (LV) tissue deficiency of EETs. Untreated ACF TGR began to die 17 days after creating ACF and were all dead by day 84. The treatment with EET-A alone or ACEi alone improved the survival rate: in 156 days after ACF creation, it was 45.5% and 59.4%, respectively. The combined treatment with EET-A and ACEi appeared to improve the final survival to 71%; however, the difference from either single treatment regimen did not reach significance. Nevertheless, our findings support the notion that targeting the cytochrome P-450-dependent epoxygenase pathway of arachidonic acid metabolism should be considered for the treatment of HF.

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Section: Series 3: Effects Of Single Treatment With Eet-a or Acei Or With A Combination Thereof On The Survival Rate And Albuminuriamentioning

confidence: 75%

Section: Heart Failure Model Exclusion Criteriamentioning

confidence: 99%

Section: Acf Tgrmentioning

confidence: 99%

Section: Acf Tgrmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Effects of Epoxyeicosatrienoic Acid-Enhancing Therapy on the Course of Congestive Heart Failure in Angiotensin II-Dependent Rat Hypertension: From mRNA Analysis towards Functional In Vivo Evaluation

et al. 2021

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A comprehensive analysis of albuminuria in canine chronic kidney disease

Paukner,

Filipejova,

Mareš

et al. 2024

Veterinary Medicine & Sci

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BackgroundAlbuminuria, an important marker of decreased kidney function in chronic kidney disease (CKD), is not routinely used for CKD detection or proteinuria appearance. Its relationships with biochemical parameters and blood pressure in dogs are poorly understood.ObjectivesThis study aimed to evaluate the relationship of albuminuria with various CKD markers, its correlation with the urinary protein to creatinine ratio (UPC), and hypertension in dogs with early stages of CKD. It also sought to determine the usability of the urinary albumin to creatinine ratio (UAC) for CKD screening.MethodsThe study reviewed records of 102 dogs, categorising them into four groups based on disease status. UAC and UPC ratio, biochemistry and haematology variables, age, and systolic blood pressure were determined.ResultsThe Pearson's correlation coefficient between log‐transformed values of UPC and UAC was r = 0.902 (95% CI: 0.87 to 0.93). Median UAC ratio values were 2.1 mg/g for the Healthy control group (n = 17), 54.2 mg/g for early stages CKD (n = 42), 5.8 mg/g for Acute sick control (n = 30), and 104 mg/g for Chronic sick control (n = 13). Thresholding UAC ratio as an indicator for impaired kidney function with the threshold of 10 mg/g (established based on the receiver operating characteristic curve) had a sensitivity 81.8%, specificity of 89.4%, positive predictive value (PPV) 90%, and negative predictive value (NPV) 80.1%. The correlation of UAC with biochemistry and haematology variables was statistically significant; for SDMA (μg/L), it was r = 0.566 and for other variables, it was weak to moderate. UAC was markedly elevated in cases of severe hypertension.ConclusionsUAC ratio was significantly different among dogs with impaired and not impaired kidney function. The correlation strength for the UAC and UPC ratios was high. UAC ratio may be a promising marker for proteinuria analysis in dogs with CKD or other kidney function alterations.

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The treatment with sGC stimulator improves survival of hypertensive rats in response to volume-overload induced by aorto-caval fistula

Gawryś

Husková

Škaroupková

et al. 2023

Naunyn-Schmiedeberg's Arch Pharmacol

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Heart failure (HF) has been declared as global pandemic and current therapies are still ineffective, especially in patients that develop concurrent cardio-renal syndrome. Considerable attention has been focused on the nitric oxide (NO)/soluble guanylyl cyclase (sGC)/cyclic guanosine monophosphate (cGMP) pathway. In the current study, we aimed to investigate the effectiveness of sGC stimulator (BAY41-8543) with the same mode of action as vericiguat, for the treatment of heart failure (HF) with cardio-renal syndrome. As a model, we chose heterozygous Ren-2 transgenic rats (TGR), with high-output heart failure, induced by aorto-caval fistula (ACF). The rats were subjected into three experimental protocols to evaluate short-term effects of the treatment, impact on blood pressure, and finally the long-term survival lasting 210 days. As control groups, we used hypertensive sham TGR and normotensive sham HanSD rats. We have shown that the sGC stimulator effectively increased the survival of rats with HF in comparison to untreated animals. After 60 days of sGC stimulator treatment, the survival was still 50% compared to 8% in the untreated rats. One-week treatment with sGC stimulator increased the excretion of cGMP in ACF TGR (109 ± 28 nnmol/12 h), but the ACE inhibitor decreased it (-63 ± 21 nnmol/12 h). Moreover, sGC stimulator caused a decrease in SBP, but this effect was only temporary (day 0: 117 ± 3; day 2: 108 ± 1; day 14: 124 ± 2 mmHg). These results support the concept that sGC stimulators might represent a valuable class of drugs to battle heart failure especially with cardio-renal syndrome, but further studies are necessary.

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Effects of renal sympathetic denervation on the course of congestive heart failure combined with chronic kidney disease: Insight from studies with fawn-hooded hypertensive rats with volume overload induced using aorto-caval fistula

Abstract: Chábová (2021): Effects of renal sympathetic denervation on the course of congestive heart failure combined with chronic kidney disease: Insight from studies with fawn-hooded hypertensive rats with volume overload induced using aorto-caval fistula, Clinical and Experimental Hypertension,

Cited by 10 publications

References 77 publications

Effects of Epoxyeicosatrienoic Acid-Enhancing Therapy on the Course of Congestive Heart Failure in Angiotensin II-Dependent Rat Hypertension: From mRNA Analysis towards Functional In Vivo Evaluation

Effects of Epoxyeicosatrienoic Acid-Enhancing Therapy on the Course of Congestive Heart Failure in Angiotensin II-Dependent Rat Hypertension: From mRNA Analysis towards Functional In Vivo Evaluation

A comprehensive analysis of albuminuria in canine chronic kidney disease

The treatment with sGC stimulator improves survival of hypertensive rats in response to volume-overload induced by aorto-caval fistula

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