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Heart Failure Drugs: β-Blockers

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β-adrenergic antagonists, commonly known as β-blockers, block the effects of sympathetic neurotransmitters such as noradrenaline (NA) and adrenaline (ADR). They have several beneficial effects in heart failure treatment. They reduce heart rate, the force of contraction, and cardiac muscle relaxation. They also slow the atrial-ventricular conduction rate and raise the threshold for arrhythmias. The concentration of β-blockers determines their effects on bronchodilation,...

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Related Experiment Video

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Mouse Electroacupuncture Fixation Device Fabrication for Electroacupuncture Pretreatment in Diabetic Cardiomyopathy Mouse Model

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BH4 Increases nNOS Activity and Preserves Left Ventricular Function in Diabetes.

Ricardo Carnicer¹, Drew Duglan¹, Klemen Ziberna¹

¹Cardiovascular Medicine (R.C., D.D., K.Z., A.R., S.R., J.N.S., S.M., R.A., E.R., S.C., C.A.L., K.M.C., B.C.), University of Oxford, Oxford United Kingdom.

Circulation Research

|January 26, 2021

Summary

Diabetic cardiomyopathy and heart failure with diastolic dysfunction can be treated by increasing myocardial tetrahydrobiopterin (BH4). This enhances glucose uptake and preserves heart function in diabetic patients.

Keywords:

cardiovascular disease glucose heart failure mice nitric oxide synthase

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Published on: January 23, 2018

Area of Science:

Cardiovascular Research
Metabolic Disorders
Molecular Medicine

Background:

Diabetic patients commonly develop heart failure with left ventricular (LV) diastolic dysfunction, lacking effective treatments.
Oxidation of tetrahydrobiopterin (BH4) and nitric oxide synthase (NOS) dysfunction are implicated in diabetic cardiomyopathy.

Purpose of the Study:

To investigate if increasing myocardial BH4 availability prevents or reverses diabetes-induced LV dysfunction.
To elucidate the mechanism by which BH4 impacts diabetic cardiomyopathy.

Main Methods:

Utilized mouse models and human myocardial samples.
Assessed LV function using echocardiography and tissue Doppler.
Investigated nNOS (neuronal NOS) role via CRISPR/Cas9 knockout.
Examined glucose uptake pathways involving GLUT-1, NO/sGC/PKG signaling in cardiomyocytes.

Main Results:

Elevated myocardial BH4 prevented or reversed LV dysfunction in diabetic mice.
BH4's protective effect was dependent on nNOS.
BH4 increased glucose uptake via GLUT-1 in cardiomyocytes, preserving mitochondrial function and energetics.
This mechanism involved a NO/sGC/PKG pathway.

Conclusions:

Myocardial BH4 prevents and reverses diabetic LV dysfunction through an nNOS-mediated increase in insulin-independent glucose uptake.
GCH1/BH4-based therapeutics show potential for treating human diabetic cardiomyopathy.