The cyclic guanosine monophosphate/B‐type natriuretic peptide ratio and mortality in advanced heart failure

Lourenço, Patrícia; Araújo, José Paulo; Azevedo, Ana; Ferreira, António; Bettencourt, Paulo

doi:10.1093/eurjhf/hfn037

Cited by 14 publications

(18 citation statements)

References 37 publications

(48 reference statements)

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“…A commercially available multi‐species cGMP EIA measurement kit5 was validated for use in this dog group by confirming intra‐assay precision (coefficient of variation <10%), dilution linearity, and spike recovery in pooled canine plasma. cGMP was measured in plasma for each of the 51 samples in duplicate by spectrophotometry and standard curve methodology as previously described 22. Samples with >10% coefficient of variation were repeated.…”

Section: Methodsmentioning

confidence: 99%

“…cGMP was measured in plasma for each of the 51 samples in duplicate by spectrophotometry and standard curve methodology as previously described. 22 Samples with >10% coefficient of variation were repeated. cGMP concentrations were separated by genotype as either wild type (matching the canine reference sequence) or polymorphic (either positive heterozygous or positive homozygous for the polymorphism).…”

Section: Methodsmentioning

confidence: 99%

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Identification of PDE5A:E90K: A Polymorphism in the Canine Phosphodiesterase 5A Gene Affecting Basal cGMP Concentrations of Healthy Dogs

Stern

Reina-Doreste

Chdid

et al. 2013

Veterinary Internal Medicne

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BackgroundCyclic guanosine monophosphate (cGMP)‐specific phosphodiesterase (PDE5A) is the target of phosphodiesterase inhibitors such as sildenafil. Polymorphisms in the PDE5A gene that may predict response to therapy with sildenafil and nitric oxide, be linked to disease progression, and aid in risk assessment have been identified in human beings. Identification of polymorphisms in PDE5A could affect the physiologic actions of PDE5A and the effects of phosphodiestrase type 5 inhibitor drugs.Hypothesis/ObjectiveFunctional polymorphisms exist in the canine PDE5A gene. Specific objectives were to identify PDE5A polymorphisms and evaluate their functional relevance.AnimalsSeventy healthy dogs.MethodsThe exonic, splice‐site, 3′ and 5′ untranslated regions of the canine PDE5A gene were sequenced in 15 dogs and aligned with the canine reference sequence. Identified polymorphisms were evaluated in 55 additional, healthy, unrelated dogs of 20 breeds. Plasma was collected from 51 of these dogs and cGMP was measured. An unpaired t‐test and one‐way ANOVA with Dunnett's test of multiple comparisons were used to evaluate the effect of genotype on cGMP.ResultsA common exonic polymorphism was identified that changed glutamic acid to lysine and resulted in significantly lower cGMP concentrations in the group with polymorphism versus the wild type group (P = .014). Additionally, 6 linked single nucleotide polymorphisms in the 3′ untranslated region were identified that did not alter cGMP concentrations.Conclusions and Clinical ImportanceA polymorphism exists in the canine PDE5A gene that is associated with variable circulating cGMP concentrations in healthy dogs and warrants investigation in diseases such as pulmonary hypertension.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Identification of PDE5A:E90K: A Polymorphism in the Canine Phosphodiesterase 5A Gene Affecting Basal cGMP Concentrations of Healthy Dogs

Stern

Reina-Doreste

Chdid

et al. 2013

Veterinary Internal Medicne

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“…The up‐regulation of BNP in response to overload is protective and considered to be a potential therapeutic tool in the treatment of heart failure (HF) . However in HF patients, the beneficial effects of BNP are not always apparent . The reason is multifactorial but may be explained in part by the presence of several BNP molecular entities in blood, each with different biological effects ,.…”

Section: Introductionmentioning

confidence: 99%

“…1 However in HF patients, the beneficial effects of BNP are not always apparent. 2 The reason is multifactorial but may be explained in part by the presence of several BNP molecular entities in blood, each with different biological effects. 3,4 Obviously, knowing how to modulate the formation of truncated BNP may have an impact on the therapeutic approach to patients with HF.…”

Section: Introductionmentioning

confidence: 99%

Dipeptidyl peptidase IV inhibition improves cardiorenal function in overpacing‐induced heart failure

Gomez¹,

Touihri²,

Matheeussen

et al. 2012

European J of Heart Fail

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AimsRecent studies indicate that brain natriuretic peptide (BNP 1 -32 ) may be truncated into BNP 3 -32 by dipeptidyl peptidase IV (DPP4) and that BNP 3 -32 has reduced biological activities compared with BNP 1 -32 . We investigated if DPP4 contributes to the cardiorenal alterations and to the attenuated response to BNP seen in heart failure. Methods and resultsHaemodynamic and renal assessment was performed in 12 pigs at baseline, 4 weeks after pacing-induced heart failure, and during BNP infusion. They were randomized to either placebo or treatment with a DPP4 inhibitor, sitagliptin. After 4 weeks of pacing, heart rate was reduced compared with baseline in the sitagliptin group (60 + 2 vs. 95 + 16 b.p.m., P , 0.01), and an increase in stroke volume was observed in the sitagliptin group compared with placebo (+24 + 6% vs. -17 + 7%, P , 0.01). Glomerular filtration rate declined at week 4 compared with baseline in the placebo group (1.3 + 0.4 vs. 2.3 + 0.3 mL/kg/min, P , 0.01) but remained preserved in the sitagliptin group [1.8 + 0.2 vs. 2.0 + 0.3 mL/kg/min, P ¼ NS (non-significant)]. In the sitagliptin group, BNP infusion improved end-systolic elastance (68 + 5 vs. 31 + 4 mmHg/kg/mL, P , 0.05), ventricular-arterial coupling, and mechanical efficiency. Compared with controls (n ¼ 6), myocardial gene expression of BNP, interleukin-6, Na + -Ca 2+ exchanger, and calmodulin was up-regulated in the placebo group, but not in the sitagliptin group. ConclusionIn pacing-induced heart failure, DPP4 inhibition preserves the glomerular filtration rate, modulates stroke volume and heart rate, and potentiates the positive inotropic effect of exogenous BNP at no energy expense.--

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“…Previously, it was suggested that dephosphorylation of the NPR-A receptor could potentially play a role in the renal hyporesponsiveness seen in HF patients (Lourenço et al 2009). However, a closer look suggested that in addition to a reduction in NPR-A protein there may also be a reduction in phosphorylated NPR-A protein in the kidney membranes of HF animals .…”

Section: Mechanisms Of Renal Hyporesponsiveness To Bnp In Heart Failurementioning

confidence: 99%

Mechanisms of renal hyporesponsiveness to BNP in heart failure

Egom¹,

Feridooni

Hotchkiss

et al. 2015

Can. J. Physiol. Pharmacol.

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The B-type natriuretic peptide (BNP), a member of the family of vasoactive peptides, is a potent natriuretic, diuretic, and vasodilatory peptide that contributes to blood pressure and volume homeostasis. These attributes make BNP an ideal drug that could aid in diuresing a fluid-overloaded patient who had poor or worsening renal function. Despite the potential benefits of BNP, accumulating evidence suggests that simply increasing the amount of circulating BNP does not necessarily increase natriuresis in patients with heart failure (HF). Moreover, despite high BNP levels, natriuresis falls when HF progresses from a compensated to a decompensated state, suggesting the emergence of renal resistance to BNP. Although likely multifactorial, several mechanisms have been proposed to explain renal hyporesponsiveness in HF, including, but not limited to, decreased renal BNP availability, down-regulation of natriuretic peptide receptors, and altered BNP intracellular signal transduction pathways. Thus, a better understanding of renal hyporesponsiveness in HF is required to devise strategies to develop novel agents and technologies that directly restore renal BNP efficiency. It is hoped that development of these new therapeutic approaches will serve to limit sodium retention in patients with HF, which may ultimately delay the progression to overt HF.

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The cyclic guanosine monophosphate/B‐type natriuretic peptide ratio and mortality in advanced heart failure

Cited by 14 publications

References 37 publications

Identification of PDE5A:E90K: A Polymorphism in the Canine Phosphodiesterase 5A Gene Affecting Basal cGMP Concentrations of Healthy Dogs

Identification of PDE5A:E90K: A Polymorphism in the Canine Phosphodiesterase 5A Gene Affecting Basal cGMP Concentrations of Healthy Dogs

Dipeptidyl peptidase IV inhibition improves cardiorenal function in overpacing‐induced heart failure

Mechanisms of renal hyporesponsiveness to BNP in heart failure

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