Chronic administration of phosphodiesterase type 5 inhibitor suppresses renal production of endothelin-1 in dogs with congestive heart failure

2002 ◽  
Vol 103 (s2002) ◽  
pp. 258S-262S ◽  
Author(s):  
Takashi YAMAMOTO ◽  
Atsuyuki WADA ◽  
Masato OHNISHI ◽  
Takayoshi TSUTAMOTO ◽  
Masanori FUJII ◽  
...  
Keyword(s):  
Heart Failure ◽  
Congestive Heart Failure ◽  
Sodium Excretion ◽  
Pde5 Inhibitor ◽  
Vehicle Group ◽  
Endothelin 1 ◽  
Phosphodiesterase Type 5 Inhibitor ◽  
Significant Difference ◽  
Phosphodiesterase Type ◽  
Renal Expression

Endothelin-1 (ET-1) and atrial natriuretic peptide (ANP) play important roles in the regulation of body fluid balance in congestive heart failure (CHF). Renal production of ET-1 increases in CHF and it is a significant independent predictor of sodium excretion. ANP inhibits the ET system through cGMP, a second messenger of ANP. However, in severe CHF, plasma cGMP levels reached a plateau despite the activation of ANP secretion. Thus, ANP does not seem to sufficiently oppose exaggerated ET-1 actions in severe CHF, partially due to the accelerated degradation of cGMP, through phosphodiesterase type 5 (PDE5). We examined the chronic effects of a PDE5 inhibitor, T-1032 (1mg/kg per day, n = 5), on renal function and renal production of ET-1 in dogs with CHF induced by rapid ventricular pacing (270beats/min). Vehicle dogs were given a placebo (n = 5) and normal dogs (n = 5) served as normal controls without pacing. In this experimentally produced CHF, plasma levels of ET-1, ANP and cGMP were elevated and renal production of cGMP was increased compared with the normal group, associated with increases in renal expression of preproET-1 mRNA and the number of ET-1-positive cells in glomeruli. In the T-1032 group, systemic and renal production of cGMP were further increased compared with the vehicle group despite no significant difference in plasma ANP levels between the two groups. Subsequently, the agent significantly improved urine flow rate, sodium excretion rate and glomerular filtration rate (GFR) associated with reductions in renal expression of preproET-1 mRNA and the number of ET-1-positive cells compared with the vehicle group. Moreover, there was a significant negative correlation between the number of ET-1-positive cells and GFR (r =-0.802 and P<0.001 respectively). Our results indicate that chronic PDE5 inhibition ameliorates the antagonistic relationship between renal ANP and ET-1 through the cGMP pathway, subsequently preventing renal dysfunction during the progression of CHF.

678 Molecular mechanisms of increased plasma endothelin-1 levels in congestive heart failure

2003 ◽  
Vol 2 (1) ◽  
pp. 139
Author(s):  
T VONLUEDER ◽  
H KJEKSHUS ◽  
T EDVARDSEN ◽  
E OIE ◽  
S URHEIM ◽  
...  
Keyword(s):  
Heart Failure ◽  
Congestive Heart Failure ◽  
Molecular Mechanisms ◽  
Endothelin 1

Endogenous Endothelin-1 Participates in the Maintenance of Cardiac Function in Rats With Congestive Heart Failure

Circulation ◽  
1996 ◽  
Vol 93 (6) ◽  
pp. 1214-1222 ◽  
Author(s):  
Satoshi Sakai ◽  
Takashi Miyauchi ◽  
Takeshi Sakurai ◽  
Yoshitoshi Kasuya ◽  
Masaki Ihara ◽  
...  
Keyword(s):  
Heart Failure ◽  
Congestive Heart Failure ◽  
Cardiac Function ◽  
Endothelin 1

Abstract 15848: Restoration of Normal Cardiomyocyte Basal and β-Adrenergic Receptor (AR) Subtype Modulation in Heart Failure by Chronic Phosphodiesterase Type 5 Inhibition With Sildenafil

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Tiankai Li ◽  
Heng-Jie Cheng ◽  
Shadi A Qasem ◽  
Michael Callahan ◽  
Wei-Min Li ◽  
...  
Keyword(s):  
Heart Failure ◽  
Adrenergic Receptor ◽  
Pde5 Inhibitor ◽  
Left Ventricular ◽  
Cell Contractility ◽  
Lv Dysfunction ◽  
Myocyte Function ◽  
Phosphodiesterase Type ◽  
Β Adrenergic Receptors ◽  
Mini Pump

Background: We have shown that Sildenafil (SIL), a selective PDE5 inhibitor reversed left ventricular (LV) dysfunction and β- adrenergic receptors (AR) desensitization in heart failure (HF). However the mechanism is not yet clear. Recent evidence suggests that normal myocardial performance depend on the balance in cardiomyocyte β 3 -, β 1 -, and β 2 -AR. Pivotal restructuring of β-AR system resulting in decline of β-adrenergic reserve plays a crucial role in the development of HF. We assessed the hypothesis that chronic SIL would prevent HF-induced abnormalities of β-AR subtype-stimulated regulation on intrinsic LV myocyte function and [Ca 2+ ] i regulation, thus restoring cardiac function. Methods: Studies were conducted in 3 groups (10/group) of rats: 1) HF, 12 weeks (W) after receiving isoproterenol (ISO) (170 mg/kg sq for 2 days); 2) HF/SIL, 8W after receiving ISO, SIL (70 μg/kg/day sq via mini pump) was initiated and given for 1 M; and 3) controls. After 12W, we compared LV myocyte contractile and [Ca 2+ ] iT responses to β-AR subtype stimulation by random exposure of myocytes to ISO (10 -8 M) or a selective β 1 -, β 2 -, or β 3 -agonist, Norepinephrine (NE, 10 -7 M), Zinterol (ZIN, 10 -5 M) and BRL-37,344 (BRL, 10 -8 M), respectively, during drug superfusion. Results: Only ISO-treated rats had HF showed 46% decreased LV contractility (E ES ) and extensive LV myocardium fibrosis. Compared with normal myocytes (N), in HF myocytes, basal cell contractility (dL/dt max , HF: 77 vs N: 136 μm/s), relaxation and [Ca 2+ ] iT all significantly decreased. ISO-stimulated dL/dt max (31% vs 67%) was attenuated accompanied by a diminished NE-mediated increase in dL/dt max (13% vs 49%), but enhanced BRL-induced decreases in dL/dt max (-29% vs -16%).The response of dL/dt max (25% vs 15%) to ZIN was increased. Importantly, in HF/SIL myocytes, the basal dL/dt max (139 μm/s) and [Ca 2+ ] iT remained close to control values with preserved β-stimulated positive modulation on cell contraction. The increases in dL/dt max in response to ISO (70%) and NE (44%) were similar as in normal myocytes, but repose to ZIN (27%) was enhanced. Conclusions: Chronic SIL reverses β-adrenergic signaling defects, resensitizing the β-AR subtype system modulation on LV myocytes function, thus playing a salutary role in HF.

scholarly journals An Echocardiographic Evaluation of Dilated Cardiomyopathy in a Tertiary Care Hospital

2019 ◽  
Vol 57 (215) ◽  
Author(s):  
Raj Kumar Thapa ◽  
Kanchan K.C ◽  
Rishi Khatri ◽  
Devendra Khatri ◽  
Rajeeb Kumar Deo ◽  
...  
Keyword(s):  
Heart Failure ◽  
Congestive Heart Failure ◽  
Left Ventricle ◽  
Ejection Fraction ◽  
Dilated Cardiomyopathy ◽  
Tertiary Care ◽  
Left Ventricular ◽  
Care Hospital ◽  
Echocardiographic Evaluation ◽  
Significant Difference

Introduction: Cardiomyopathies are diseases of heart muscle that may originate from genetic defects, cardiac myocyte injury or infiltration of myocardial tissues. Dilated cardiomyopathy is the most common phenotype and is often a final common pathway of numerous cardiac insults. Mostly it remains unknown in the absence of echocardiography, histopathology and genetic evaluation. Though common it is underdiagnosed with not much of data available in our setup.Methods: This study was analytical cross-sectional study of hospital data on Echocardiographic findings in 65 patients of DCM visiting cardiology unit for Echocardiographic evaluation from 1st of February to 31st July 2018 for the period of six months in Shree Birendra Hospital, a tertiary care military hospital at Chhauni, Kathmandu. Pediatric age group patients and those who refused to give consent were excluded. Data obtained were entered in Microsoft Excel 2010 and analyzed by IBM SPSS 21.Results: Among 65 patients enrolled 40 (61%) were male and 25 (39%) female with male to female ratio of 1.6:1. Elderly people (61-75 years) with an average age of 65 were commonly involved and they presented mostly with congestive heart failure, 32 (49%). Echocardiographic evaluation showed 36 (55%) with mildly dilated Left Ventricle (5.6-6.0cm). Majority had reduced Left ventricular systolic function with an average Ejection fraction (EF) of 39.6%. No significant difference between male and female with the average EF% (P=0.990) and there was no significant relation between age and average EF% (P=0.091).Conclusions: Dilated Cardiomyopathy is the commonest cardiomyopathy phenotype mostly presenting with congestive heart failure. It is often underdiagnosed in our part of the world, however echocardiography will easily detect the condition. Keywords: dilated cardiomyopathy; echocardiography; ejection fraction; left ventricle.

scholarly journals Degenerative Pathology of the Ankle, Hindfoot, and Midfoot is as Limiting to Patient Mobility as Congestive Heart Failure

2019 ◽  
Vol 4 (4) ◽  
pp. 2473011419S0016
Author(s):  
Amalie Erwood ◽  
Gregory Kurkis ◽  
Samuel David Maidman ◽  
Robert Cole ◽  
Shay Ariel Tenenbaum ◽  
...  
Keyword(s):  
Heart Failure ◽  
Congestive Heart Failure ◽  
Nyha Class ◽  
Class Ii ◽  
Study Patient ◽  
Foot And Ankle ◽  
Ankle Arthritis ◽  
Patient Mobility ◽  
Patient Demographics ◽  
Significant Difference

Category: Ankle, Ankle Arthritis, Hindfoot, Midfoot/Forefoot Introduction/Purpose: Degenerative conditions of the ankle, hindfoot, and midfoot can markedly limit mobility. The Life-Space Assessment (LSA) is a questionnaire quantifying how patients mobilize after a medical event as they return to their previous daily settings. Current outcome measures do not accurately assess mobility in the geriatric foot and ankle population. In contrast, the effect of congestive heart failure (CHF) on patient mobility is routinely assessed via the New York Heart Association (NYHA) functional classification. The NYHA classification is stratified by limitation of physical activity: I (no limitation), II (some limitation), III (marked limitation), and IV (unable to carry out without discomfort). We hypothesized that degenerative conditions of the foot and ankle would be as mobility limiting as CHF. Methods: Patients over the age of 50 were included in this study. LSA data was prospectively collected from patients with degenerative ankle, hindfoot, and midfoot diagnoses at their preoperative visit and NYHA-classified CHF patients at a cardiology clinic. The degenerative foot and ankle cohort included Achilles tendonitis, ankle joint cartilage defects, ankle arthritis, subtalar arthritis, and midfoot arthritis. Patient demographics and comorbidities were recorded from the electronic medical record. Mean LSA data was analyzed and compared using a Student’s t-test. Results: 28 degenerative foot and ankle patients and 44 CHF patients met inclusion criteria for the study. Patient demographics, including age, gender, and BMI, were not significantly different between the two groups. The foot and ankle cohort had a mean LSA score of 68. Mobility of the foot and ankle group was significantly less compared to NYHA class I patients, who had a LSA score of 103 (p=0.008). There was no significant difference in mobility compared to class II or III congestive heart failure patients, who recorded a mean LSA score of 62 (p=0.60). There was insufficient data available on NYHA class IV patients to make comparisons to this group. Conclusion: Degenerative ankle, hindfoot, and midfoot pathology is associated with similar mobility limitation to that of NYHA class II and III congestive heart failure.

scholarly journals Audiometry Results and TEOAE and DPOAE Amplitudes in Men Taking a Phosphodiesterase Type 5 Inhibitor for Erectile Dysfunction

2017 ◽  
Vol 96 (7) ◽  
pp. E34-E39 ◽  
Author(s):  
Sertan Öntepeli ◽  
Nuray Bayar Muluk ◽  
Devrim Tuğlu ◽  
Timuçin Şipal
Keyword(s):  
Erectile Dysfunction ◽  
Otoacoustic Emissions ◽  
Pde5 Inhibitor ◽  
Post Treatment ◽  
Guanosine Monophosphate ◽  
Pde5 Inhibitors ◽  
Cochlear Blood Flow ◽  
Distortion Product ◽  
Phosphodiesterase Type 5 Inhibitor ◽  
Phosphodiesterase Type

We conducted a prospective study of transient evoked otoacoustic emissions (TEOAEs) and distortion-product otoacoustic emissions (DPOAEs) in men who were taking an oral phosphodiesterase type 5 (PDE5) inhibitor for erectile dysfunction. Our study group was made up of 30 men (60 ears), aged 34 to 60 years (mean: 50.9). They were randomly divided into three groups; 10 men were given sildenafil (Viagra) at 50 mg twice a week, 10 were given tadalafil (Cialis) at 20 mg twice a week, and 10 were given vardenafil (Levitra) at 20 mg twice a week. All patients took their drug for 3 weeks, for a total of 6 tablets for each patient. Audiometric tests and TEOAE and DPOAE measurements were performed before and after treatment. Post-treatment audiometry demonstrated improvement in hearing in all three groups. However, post-treatment TEOAE amplitudes and DPOAE amplitudes differed among the three groups; they were significantly higher in the sildenafil group at 1.0 kHz and the same in the tadalafil group; in the vardenafil group, the DPOAE amplitude was significantly lower at 3.0 kHz while there was no change in the TEOAE amplitude. We speculate that the possible mechanism for these findings is that PDE5 inhibitors block degradation of cyclic guanosine monophosphate (cGMP) and induce dilation of the cochlear microcirculation, resulting in an increase in cochlear blood flow. We also believe that the decrease in DPOAE amplitudes at 3.0 kHz seen in the vardenafil group may be related to an accumulation of nitric oxide/cGMP complex, which is toxic to the cochlea; however, since there was no change in TEOAE amplitude in the vardenafil group, this influence may be minimal. Further studies are needed to obtain a more comprehensive assessment of the effects of PDE5 inhibitors on hearing with the use of higher doses and longer durations of therapy.

Captopril does not acutely modulate plasma endothelin-1 concentration in human congestive heart failure

1996 ◽  
Vol 10 (5) ◽  
pp. 561-565 ◽  
Author(s):  
O. Grenier ◽  
F. Pousset ◽  
R. Isnard ◽  
H. Kalotka ◽  
A. Carayon ◽  
...  
Keyword(s):  
Heart Failure ◽  
Congestive Heart Failure ◽  
Endothelin 1
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