February 8, 2023Journal of the American Heart AssociationOpen Access

Treatment with sodium nitrite and hydralazine restored NO bioavailability, reduced oxidative and nitrosative stress, preserved endothelial function and mitochondrial respiration, limited the fibrotic response, and improved exercise capacity.

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Why the study?

Conflicting evidence links both pathological NO overproduction and attenuated NO bioavailability to HFpEF, prompting investigation of dysregulated NO signaling and NO-based dual therapy.

Does combination sodium nitrite and hydralazine therapy attenuate HFpEF severity in a 2-hit murine model?

Population

Nine-week-old male C57BL/6 N mice (n=15 per group) in a 2-hit HFpEF model

Comparison

Sodium nitrite plus hydralazine vs vehicle (normal saline)

Design

Randomized preclinical animal study

Follow-up

10 weeks

Authors

KLKyle B. LaPenna ZLZhen Li JDJake E. Doiron

Discussion

Member takes

Overview

Targeting NO pathways in HFpEF should not yet change practice; leaves open optimal iNOS or eNOS targets.

Structured PICO

Does combination sodium nitrite and hydralazine therapy attenuate HFpEF severity in a 2-hit murine model?

Population

9-week-old male C57BL/6 N mice (n=15 per group) treated concurrently with high-fat diet and N(ω)-nitro-L-arginine methyl ester (L-NAME) (0.5 g/L per day) via drinking water for 10 weeks to induce a '2-hit' HFpEF model.

Intervention

Combination treatment with sodium nitrite (75 mg/L in the drinking water) and hydralazine (2.0 mg/kg IP, BID) starting at week 5.

Comparator

Vehicle (normal saline).

Outcome

Cardiac structure and function (echocardiography and invasive hemodynamics), cardiac mitochondrial respiration, aortic vascular function, exercise performance, and NO bioavailability.surrogate

In a murine model of HFpEF, combination therapy with sodium nitrite and hydralazine attenuated disease severity by restoring NO bioavailability and reducing oxidative stress.

Cite This Study

LaPenna et al. (2023) studied this question.

synapsesocial.com/papers/6a7d453b560d7d74ed46cc72 https://doi.org/10.1161/jaha.122.028480

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February 8, 2023Journal of the American Heart AssociationOpen Access

Treatment with sodium nitrite and hydralazine restored NO bioavailability, reduced oxidative and nitrosative stress, preserved endothelial function and mitochondrial respiration, limited the fibrotic response, and improved exercise capacity.

View Full Paper

Ask AI

Bookmark

Why the study?

Conflicting evidence links both pathological NO overproduction and attenuated NO bioavailability to HFpEF, prompting investigation of dysregulated NO signaling and NO-based dual therapy.

Does combination sodium nitrite and hydralazine therapy attenuate HFpEF severity in a 2-hit murine model?

Population

Nine-week-old male C57BL/6 N mice (n=15 per group) in a 2-hit HFpEF model

Comparison

Sodium nitrite plus hydralazine vs vehicle (normal saline)

Design

Randomized preclinical animal study

Follow-up

10 weeks

Authors

KLKyle B. LaPenna ZLZhen Li JDJake E. Doiron

Discussion

Member takes

Overview

Targeting NO pathways in HFpEF should not yet change practice; leaves open optimal iNOS or eNOS targets.

Structured PICO

Does combination sodium nitrite and hydralazine therapy attenuate HFpEF severity in a 2-hit murine model?

Population

Intervention

Combination treatment with sodium nitrite (75 mg/L in the drinking water) and hydralazine (2.0 mg/kg IP, BID) starting at week 5.

Comparator

Vehicle (normal saline).

Outcome

Cardiac structure and function (echocardiography and invasive hemodynamics), cardiac mitochondrial respiration, aortic vascular function, exercise performance, and NO bioavailability.surrogate

In a murine model of HFpEF, combination therapy with sodium nitrite and hydralazine attenuated disease severity by restoring NO bioavailability and reducing oxidative stress.

Cite This Study

LaPenna et al. (2023) studied this question.

synapsesocial.com/papers/6a7d453b560d7d74ed46cc72 https://doi.org/10.1161/jaha.122.028480

View Full Paper

Ask AI

Bookmark