Usage Information

Nitric oxide–sensitive guanylyl cyclase stimulation improves experimental heart failure with preserved ejection fraction
Nicola Wilck, … , Ralf Dechend, Nadine Haase
Nicola Wilck, … , Ralf Dechend, Nadine Haase
Published February 22, 2018
Citation Information: JCI Insight. 2018;3(4):e96006. https://doi.org/10.1172/jci.insight.96006.
View: Text | PDF
Research Article Cardiology Article has an altmetric score of 6

Nitric oxide–sensitive guanylyl cyclase stimulation improves experimental heart failure with preserved ejection fraction

Abstract

Heart failure with preserved ejection fraction (HFpEF) can arise from cardiac and vascular remodeling processes following long-lasting hypertension. Efficacy of common HF therapeutics is unsatisfactory in HFpEF. Evidence suggests that stimulators of the nitric oxide–sensitive soluble guanylyl cyclase (NOsGC) could be of use here. We aimed to characterize the complex cardiovascular effects of NOsGC stimulation using NO-independent stimulator BAY 41-8543 in a double-transgenic rat (dTGR) model of HFpEF. We show a drastically improved survival rate of treated dTGR. We observed less cardiac fibrosis, macrophage infiltration, and gap junction remodeling in treated dTGR. Microarray analysis revealed that treatment of dTGR corrected the dysregulateion of cardiac genes associated with fibrosis, inflammation, apoptosis, oxidative stress, and ion channel function toward an expression profile similar to healthy controls. Treatment reduced systemic blood pressure levels and improved endothelium-dependent vasorelaxation of resistance vessels. Further comprehensive in vivo phenotyping showed an improved diastolic cardiac function, improved hemodynamics, and less susceptibility to ventricular arrhythmias. Short-term BAY 41-8543 application in isolated untreated transgenic hearts with structural remodeling significantly reduced the occurrence of ventricular arrhythmias, suggesting a direct nongenomic role of NOsGC stimulation on excitation. Thus, NOsGC stimulation was highly effective in improving several HFpEF facets in this animal model, underscoring its potential value for patients.

Authors

Nicola Wilck, Lajos Markó, András Balogh, Kristin Kräker, Florian Herse, Hendrik Bartolomaeus, István A. Szijártó, Maik Gollasch, Nadine Reichhart, Olaf Strauss, Arnd Heuser, Damian Brockschnieder, Axel Kretschmer, Ralf Lesche, Florian Sohler, Johannes-Peter Stasch, Peter Sandner, Friedrich C. Luft, Dominik N. Müller, Ralf Dechend, Nadine Haase

×

Usage data is cumulative from March 2024 through March 2025.

Usage JCI PMC
Text version 648 113
PDF 72 35
Figure 231 7
Table 53 0
Supplemental data 50 6
Citation downloads 55 0
Totals 1,109 161
Total Views 1,270
(Click and drag on plot area to zoom in. Click legend items above to toggle)

Usage information is collected from two different sources: this site (JCI) and Pubmed Central (PMC). JCI information (compiled daily) shows human readership based on methods we employ to screen out robotic usage. PMC information (aggregated monthly) is also similarly screened of robotic usage.

Various methods are used to distinguish robotic usage. For example, Google automatically scans articles to add to its search index and identifies itself as robotic; other services might not clearly identify themselves as robotic, or they are new or unknown as robotic. Because this activity can be misinterpreted as human readership, data may be re-processed periodically to reflect an improved understanding of robotic activity. Because of these factors, readers should consider usage information illustrative but subject to change.

Advertisement