Capillary hemodynamics and contracting skeletal muscle oxygen pressures in male rats with heart failure: Impact of soluble guanylyl cyclase activator

Nitric Oxide ◽  
2021 ◽  
Author(s):  
Ramona E. Weber ◽  
Kiana M. Schulze ◽  
Trenton D. Colburn ◽  
Andrew G. Horn ◽  
K. Sue Hageman ◽  
...  
Keyword(s):  
Heart Failure ◽  
Skeletal Muscle ◽  
Guanylyl Cyclase ◽  
Soluble Guanylyl Cyclase ◽  
Male Rats ◽  
Muscle Oxygen ◽  
Cyclase Activator

scholarly journals Contracting Skeletal Muscle Oxygen Pressures in Rats with Heart Failure: Impact of Soluble Guanylyl Cyclase Activator

2021 ◽  
Vol 35 (S1) ◽  
Author(s):  
Ramona Weber ◽  
Kiana Schulze ◽  
Trenton Colburn ◽  
Andrew Horn ◽  
K. Sue Hageman ◽  
...  
Keyword(s):  
Heart Failure ◽  
Skeletal Muscle ◽  
Guanylyl Cyclase ◽  
Soluble Guanylyl Cyclase ◽  
Muscle Oxygen ◽  
Cyclase Activator

Soothing the sleeping giant: improving skeletal muscle oxygen kinetics and exercise intolerance in HFpEF

2015 ◽  
Vol 119 (6) ◽  
pp. 734-738 ◽  
Author(s):  
Satyam Sarma ◽  
Benjamin D. Levine
Keyword(s):  
Heart Failure ◽  
Skeletal Muscle ◽  
Oxygen Consumption ◽  
Functional Capacity ◽  
Oxidative Capacity ◽  
Exercise Intolerance ◽  
Aerobic Performance ◽  
Muscle Oxygen ◽  
Oxygen Kinetics ◽  
Patients With Heart Failure

Patients with heart failure with preserved ejection fraction (HFpEF) have similar degrees of exercise intolerance and dyspnea as patients with heart failure with reduced EF (HFrEF). The underlying pathophysiology leading to impaired exertional ability in the HFpEF syndrome is not completely understood, and a growing body of evidence suggests “peripheral,” i.e., noncardiac, factors may play an important role. Changes in skeletal muscle function (decreased muscle mass, capillary density, mitochondrial volume, and phosphorylative capacity) are common findings in HFrEF. While cardiac failure and decreased cardiac reserve account for a large proportion of the decline in oxygen consumption in HFrEF, impaired oxygen diffusion and decreased skeletal muscle oxidative capacity can also hinder aerobic performance, functional capacity and oxygen consumption (V̇o2) kinetics. The impact of skeletal muscle dysfunction and abnormal oxidative capacity may be even more pronounced in HFpEF, a disease predominantly affecting the elderly and women, two demographic groups with a high prevalence of sarcopenia. In this review, we 1) describe the basic concepts of skeletal muscle oxygen kinetics and 2) evaluate evidence suggesting limitations in aerobic performance and functional capacity in HFpEF subjects may, in part, be due to alterations in skeletal muscle oxygen delivery and utilization. Improving oxygen kinetics with specific training regimens may improve exercise efficiency and reduce the tremendous burden imposed by skeletal muscle upon the cardiovascular system.

scholarly journals Effects of the soluble guanylyl cyclase activator, YC-1, on vascular tone, cyclic GMP levels and phosphodiesterase activity

1999 ◽  
Vol 127 (1) ◽  
pp. 195-203 ◽  
Author(s):  
Jan Galle ◽  
Ulrike Zabel ◽  
Ulrich Hübner ◽  
Armin Hatzelmann ◽  
Birgit Wagner ◽  
...  
Keyword(s):  
Cyclic Gmp ◽  
Guanylyl Cyclase ◽  
Vascular Tone ◽  
Soluble Guanylyl Cyclase ◽  
Phosphodiesterase Activity ◽  
Cyclase Activator

Abstract 556: The Soluble Guanylyl Cyclase Activator Bay 60-2770 Inhibits Arterial Smooth Muscle Cell Migration in Protein Kinase G-dependent Manner

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Andrew Holt ◽  
Danielle Martin ◽  
Patti Shaver ◽  
Shaquria Adderley ◽  
Joshua Stone ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Cell Migration ◽  
Protein Kinase ◽  
Cyclic Gmp ◽  
Guanylyl Cyclase ◽  
Soluble Guanylyl Cyclase ◽  
Protein Kinase G ◽  
Growth Disorders ◽  
Arterial Smooth Muscle ◽  
Cyclase Activator

Atherosclerotic lower extremity peripheral artery disease (PAD) is among the most prevalent, morbid and mortal of all cardiovascular disorders. Pathologic arterial smooth muscle (ASM) cell migration is a major component of atherogenic PAD and efforts aimed at attenuating its progression are clinically essential. Cyclic nucleotide signaling has long been studied for its growth-mitigating properties in the setting of PAD and other vascular growth disorders. In this study we hypothesized that the novel, heme-independent soluble guanylyl cyclase activator BAY 60-2770 (BAY) inhibits ASM cell migration through phosphorylation of the protein kinase G (PKG) target and actin-binding protein vasodilator-stimulated phosphoprotein (VASP). In a rat model of injury-induced arterial growth, BAY significantly reduced neointima formation and luminal narrowing compared to vehicle (Veh)-treated control arteries after 2 weeks. Using rat and human ASM cells BAY significantly attenuated cell migration, reduced G:F actin, and increased cyclic GMP content, PKG activity and phosphorylated VASP at Ser239 (pVASP.S239) compared to Veh controls. Using site-directed mutagenesis, both full-length VASP-overexpressing (wild type, WT) and VASP.S239 phosphorylation-resistant mutants showed significantly reduced cell migration compared to naïve controls, however, there was no effect on cell migration between either VASP transfected group in the presence of BAY. Interestingly, both VASP mutants showed significantly increased PKG activity compared to naïve cells, and in turn pharmacologic PKG blockade in the presence of BAY fully reversed the inhibitory effect of BAY alone on cell migration. These data suggest BAY has capacity to inhibit ASM cell migration through cyclic GMP/PKG/VASP signaling yet through mechanisms independent of pVASP.S239. Findings from this study implicate BAY via cyclic GMP/PKG/VASP as a potential pharmacotherapeutic agent against aberrant ASM growth disorders such as PAD.

The soluble guanylyl cyclase activator BAY 60-2770 potently relaxes the pulmonary artery on congenital diaphragmatic hernia rabbit model

2014 ◽  
Vol 30 (10) ◽  
pp. 1031-1036 ◽  
Author(s):  
Julio Alejandro Rojas-Moscoso ◽  
Edson Antunes ◽  
Rebeca Rodrigues Figueira ◽  
Frances Lilian Gonçalves ◽  
Ana Leda Bertoncioni Simões ◽  
...  
Keyword(s):  
Pulmonary Artery ◽  
Congenital Diaphragmatic Hernia ◽  
Diaphragmatic Hernia ◽  
Guanylyl Cyclase ◽  
Rabbit Model ◽  
Soluble Guanylyl Cyclase ◽  
Cyclase Activator

scholarly journals The Soluble Guanylyl Cyclase Activator Bay 58-2667 Selectively Limits Cardiomyocyte Hypertrophy

PLoS ONE ◽  
2012 ◽  
Vol 7 (11) ◽  
pp. e44481 ◽  
Author(s):  
Jennifer C. Irvine ◽  
Virat Ganthavee ◽  
Jane E. Love ◽  
Amy E. Alexander ◽  
John D. Horowitz ◽  
...  
Keyword(s):  
Guanylyl Cyclase ◽  
Soluble Guanylyl Cyclase ◽  
Cardiomyocyte Hypertrophy ◽  
Cyclase Activator

The soluble guanylyl cyclase activator BAY 60-2770 inhibits murine allergic airways inflammation and human eosinophil chemotaxis

2016 ◽  
Vol 41 ◽  
pp. 86-95 ◽  
Author(s):  
Lineu Baldissera Jr ◽  
Dalize M. Squebola-Cola ◽  
Marina C. Calixto ◽  
Ana P. Lima-Barbosa ◽  
André L. Rennó ◽  
...  
Keyword(s):  
Guanylyl Cyclase ◽  
Soluble Guanylyl Cyclase ◽  
Human Eosinophil ◽  
Eosinophil Chemotaxis ◽  
Cyclase Activator ◽  
Airways Inflammation

scholarly journals Dietary nitrate supplementation: impact on skeletal muscle vascular control in exercising rats with chronic heart failure

2016 ◽  
Vol 121 (3) ◽  
pp. 661-669 ◽  
Author(s):  
Scott K. Ferguson ◽  
Clark T. Holdsworth ◽  
Trenton D. Colburn ◽  
Jennifer L. Wright ◽  
Jesse C. Craig ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Skeletal Muscle ◽  
Mean Arterial Pressure ◽  
Chronic Heart Failure ◽  
Arterial Pressure ◽  
Vascular Function ◽  
Left Ventricular ◽  
Male Rats ◽  
Dietary Nitrate

Chronic heart failure (CHF) results in central and peripheral derangements that ultimately reduce skeletal muscle O2 delivery and impair exercise tolerance. Dietary nitrate (NO3−) supplementation improves skeletal muscle vascular function and tolerance to exercise. We tested the hypothesis that NO3− supplementation would elevate exercising skeletal muscle blood flow (BF) and vascular conductance (VC) in CHF rats. Myocardial infarction (MI) was induced (coronary artery ligation) in young adult male rats. After 21 days of recovery, rats randomly received 5 days of NO3−-rich beetroot juice (CHF + BR, n = 10) or a placebo (CHF, n = 10). Mean arterial pressure (carotid artery catheter) and skeletal muscle BF (radiolabeled microspheres) were measured during treadmill exercise (20 m/min, 5% grade). CHF-induced dysfunction, as determined by myocardial infarction size (29 ± 3% and 33 ± 4% in CHF and CHF + BR, respectively) and left ventricular end-diastolic pressure (18 ± 2 and 18 ± 2 mmHg in CHF and CHF + BR, respectively), and exercising mean arterial pressure (131 ± 3 and 128 ± 4 mmHg in CHF and CHF + BR, respectively) were not different ( P > 0.05) between groups. Total exercising hindlimb skeletal muscle BF (95 ± 5 and 116 ± 9 ml·min−1·100 g−1 in CHF and CHF + BR, respectively) and VC (0.75 ± 0.05 and 0.90 ± 0.05 ml·min−1·100 g−1·mmHg−1 in CHF and CHF + BR, respectively) were 22% and 20% greater in BR-supplemented rats, respectively ( P < 0.05). During exercise, BF in 9 and VC in 10 hindlimb muscles and muscle portions were significantly greater in the CHF + BR group. These results provide strong evidence that dietary NO3− supplementation improves skeletal muscle vascular function during exercise in rats with CHF and, thus, support the use of BR as a novel therapeutic modality for the treatment of CHF.

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