Histidine dipeptides are key regulators of excitation-contraction coupling in cardiac muscle: Evidence from a novel CARNS1 knockout rat model.

Gonçalves LS, Sales LP, Saito TR, Campos JC, Fernandes AL, Natali J, Jensen L, Arnold A, Ramalho L, Bechara LRG, Esteca MV, Correa I and 13 more

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Sant'Anna D, Ceroni A, Michelini LC, Gualano B, Teodoro W, Carvalho VH, Vargas BS, Medeiros MHG, Baptista IL, Irigoyen MC, Sale C, Ferreira JCB, Artioli GG

Redox biology20 May 2021Cited by 19 (Europe PMC)

PMID34038814PMCIDPMC8144739DOI10.1016/j.redox.2021.102016PepBankPUB-34038814

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Summary

The text of this summary is not shown here, because the article license does not allow reuse. Read it at the source (opens in a new tab)

Text rights: CC BY-NC-ND. Results still quote short attributed sentences.

Results from this study12

1 result from studies that gave the peptide. No result from this study comes from people.

01AnimalAnimal study (in vivo)Efficacy outcome
In rats, carnosine supplementation produced no relevant increase in muscle carnosine content.
In plain wordsIn rats, carnosine supplementation did not meaningfully increase muscle carnosine.
Peptide
L-carnosine
Outcome
No significant changeMuscle carnosine content
Study
ratn: not reported in source
CARNS1 knockout rats
Outcome group
Pharmacokinetics · Musculoskeletal
Studied dose
1.8% in drinking water · oral · 12 weeksAs given in this study (rat).
Source sentences
Summary
No relevant increases in muscle carnosine content were observed after carnosine supplementation.
2 context sentences(design, population, supporting numbers)
Summary · context
Animals were supplemented with carnosine (1.8% in drinking water for 12 weeks) in an attempt to rescue tissue HCDs levels and function.
Summary · context
Male wild-type (WT) and knockout rats (4 months-old) were used.
Report a problemFND-3403881411

Studies that did not test the peptide alone11

In this study, L-carnosine was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking L-carnosine.

02AnimalNot a test of L-carnosine aloneAnimal study (in vivo)Efficacy outcome
In rats, CARNS1 knockout did not affect exercise capacity versus wild type.
In plain wordsIn rats, CARNS1 knockout did not change exercise capacity compared with wild type.
Peptide
L-carnosine
Outcome
No significant changeExercise capacity
Study
ratn: not reported in source
CARNS1 knockout rats
Comparator
Wild-type rats
Outcome group
Exercise and physical function · Musculoskeletal
Source sentences
Summary
CARNS1^-/- resulted in the complete absence of carnosine and anserine, but it did not affect exercise capacity, skeletal muscle force production, fatigability or buffering capacity in vitro, indicating that these are not essential for pH regulation and function in skeletal muscle.
1 context sentence(design, population, supporting numbers)
Summary · context
Male wild-type (WT) and knockout rats (4 months-old) were used.
In this study, L-carnosine was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking L-carnosine.
Report a problemFND-3403881401
03AnimalNot a test of L-carnosine aloneAnimal study (in vivo)Efficacy outcome
In rats, CARNS1 knockout did not affect skeletal muscle force production versus wild type.
In plain wordsIn rats, CARNS1 knockout did not change muscle force compared with wild type.
Peptide
L-carnosine
Outcome
No significant changeSkeletal muscle force
Study
ratn: not reported in source
CARNS1 knockout rats
Comparator
Wild-type rats
Outcome group
Exercise and physical function · Musculoskeletal
Source sentences
Summary
CARNS1^-/- resulted in the complete absence of carnosine and anserine, but it did not affect exercise capacity, skeletal muscle force production, fatigability or buffering capacity in vitro, indicating that these are not essential for pH regulation and function in skeletal muscle.
1 context sentence(design, population, supporting numbers)
Summary · context
Male wild-type (WT) and knockout rats (4 months-old) were used.
In this study, L-carnosine was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking L-carnosine.
Report a problemFND-3403881402
04AnimalNot a test of L-carnosine aloneAnimal study (in vivo)Efficacy outcome
In rats, CARNS1 knockout did not affect skeletal muscle fatigability versus wild type.
In plain wordsIn rats, CARNS1 knockout did not change muscle fatigability compared with wild type.
Peptide
L-carnosine
Outcome
No significant changeMuscle fatigability
Study
ratn: not reported in source
CARNS1 knockout rats
Comparator
Wild-type rats
Outcome group
Exercise and physical function · Musculoskeletal
Source sentences
Summary
CARNS1^-/- resulted in the complete absence of carnosine and anserine, but it did not affect exercise capacity, skeletal muscle force production, fatigability or buffering capacity in vitro, indicating that these are not essential for pH regulation and function in skeletal muscle.
1 context sentence(design, population, supporting numbers)
Summary · context
Male wild-type (WT) and knockout rats (4 months-old) were used.
In this study, L-carnosine was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking L-carnosine.
Report a problemFND-3403881403
05AnimalNot a test of L-carnosine aloneAnimal study (in vivo)Efficacy outcome
In rats, CARNS1 knockout impaired cardiac contractile function versus wild type.
In plain wordsIn rats, CARNS1 knockout impaired heart contraction compared with wild type.
Peptide
L-carnosine
Outcome
DecreaseCardiac contractile function
Study
ratn: not reported in source
CARNS1 knockout rats
Comparator
Wild-type rats
Outcome group
Heart function · Cardiovascular
Source sentences
Summary
In cardiac muscle, however, CARNS1^-/- resulted in a significant impairment of contractile function, which was confirmed both in vivo and ex vivo in isolated sarcomeres.
1 context sentence(design, population, supporting numbers)
Summary · context
Male wild-type (WT) and knockout rats (4 months-old) were used.
In this study, L-carnosine was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking L-carnosine.
Report a problemFND-3403881405
06AnimalNot a test of L-carnosine aloneAnimal study (in vivo)Efficacy outcome
In rat cardiac muscle, CARNS1 knockout did not increase oxidative stress markers.
In plain wordsIn rats, CARNS1 knockout did not increase heart muscle oxidative stress markers.
Peptide
L-carnosine
Outcome
No significant changeOxidative stress markers
Study
ratn: not reported in source
CARNS1 knockout rats
Comparator
Wild-type rats
Outcome group
Oxidative stress · Cardiovascular
Source sentences
Summary
Impaired systolic and diastolic dysfunction were accompanied by reduced intracellular Ca²⁺ peaks and slowed Ca²⁺ removal, but not by increased markers of oxidative stress or impaired mitochondrial respiration.
1 context sentence(design, population, supporting numbers)
Summary · context
Male wild-type (WT) and knockout rats (4 months-old) were used.
In this study, L-carnosine was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking L-carnosine.
Report a problemFND-3403881409
07AnimalNot a test of L-carnosine aloneAnimal study (in vivo)Efficacy outcome
In rat cardiac muscle, CARNS1 knockout did not impair mitochondrial respiration.
In plain wordsIn rats, CARNS1 knockout did not impair heart muscle mitochondrial respiration.
Peptide
L-carnosine
Outcome
No significant changeMitochondrial respiration
Study
ratn: not reported in source
CARNS1 knockout rats
Comparator
Wild-type rats
Outcome group
Mitochondrial function · Cardiovascular
Source sentences
Summary
Impaired systolic and diastolic dysfunction were accompanied by reduced intracellular Ca²⁺ peaks and slowed Ca²⁺ removal, but not by increased markers of oxidative stress or impaired mitochondrial respiration.
1 context sentence(design, population, supporting numbers)
Summary · context
Male wild-type (WT) and knockout rats (4 months-old) were used.
In this study, L-carnosine was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking L-carnosine.
Report a problemFND-3403881410
08AnimalNot a test of L-carnosine aloneAnimal study (in vivo)Mechanism
In rats, CARNS1 knockout resulted in the complete absence of carnosine and anserine.
In plain wordsIn rats, CARNS1 knockout resulted in the complete absence of carnosine and anserine.
Peptide
L-carnosine
Outcome
DecreaseAbsence of muscle carnosine and anserine
Study
ratn: not reported in source
CARNS1 knockout rats
Outcome group
Receptor activity and mechanism · Musculoskeletal
Source sentences
Summary
CARNS1^-/- resulted in the complete absence of carnosine and anserine, but it did not affect exercise capacity, skeletal muscle force production, fatigability or buffering capacity in vitro, indicating that these are not essential for pH regulation and function in skeletal muscle.
1 context sentence(design, population, supporting numbers)
Summary · context
To investigate the in vivo roles of HCDs, we developed the first carnosine synthase knockout (CARNS1^-/-) rat strain to investigate the impact of an absence of HCDs on skeletal and cardiac muscle function.
In this study, L-carnosine was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking L-carnosine.
Report a problemFND-3403881412
09LabNot a test of L-carnosine aloneEx vivo tissueEfficacy outcome
In rat muscle tested in vitro, CARNS1 knockout did not affect buffering capacity versus wild type.
In plain wordsIn lab tests, muscle from knockout rats showed unchanged buffering capacity compared with wild type.
Peptide
L-carnosine
Outcome
No significant changeMuscle buffering capacity
Study
ratn: not reported in source
CARNS1 knockout rats
Comparator
Wild-type rats
Outcome group
Exercise and physical function · Musculoskeletal
Source sentences
Summary
CARNS1^-/- resulted in the complete absence of carnosine and anserine, but it did not affect exercise capacity, skeletal muscle force production, fatigability or buffering capacity in vitro, indicating that these are not essential for pH regulation and function in skeletal muscle.
1 context sentence(design, population, supporting numbers)
Summary · context
Male wild-type (WT) and knockout rats (4 months-old) were used.
In this study, L-carnosine was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking L-carnosine.
Report a problemFND-3403881404
10LabNot a test of L-carnosine aloneEx vivo tissueEfficacy outcome
In isolated rat sarcomeres, CARNS1 knockout impaired contractile function versus wild type.
In plain wordsIn lab tests, isolated sarcomeres from knockout rats showed impaired contraction compared with wild type.
Peptide
L-carnosine
Outcome
DecreaseIsolated sarcomere contractile function
Study
ratn: not reported in source
CARNS1 knockout rats
Comparator
Wild-type rats
Outcome group
Heart function · Cardiovascular
Source sentences
Summary
In cardiac muscle, however, CARNS1^-/- resulted in a significant impairment of contractile function, which was confirmed both in vivo and ex vivo in isolated sarcomeres.
1 context sentence(design, population, supporting numbers)
Summary · context
Male wild-type (WT) and knockout rats (4 months-old) were used.
In this study, L-carnosine was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking L-carnosine.
Report a problemFND-3403881406
11LabNot a test of L-carnosine aloneEx vivo tissueMechanism
In rat cardiomyocytes, CARNS1 knockout accompanied reduced intracellular calcium peaks.
In plain wordsIn lab tests, knockout rat heart cells showed lower calcium peaks than wild-type cells.
Peptide
L-carnosine
Outcome
DecreaseIntracellular calcium peaks
Study
ratn: not reported in source
CARNS1 knockout rats
Comparator
Wild-type rats
Outcome group
Heart function · Cardiovascular
Source sentences
Summary
Impaired systolic and diastolic dysfunction were accompanied by reduced intracellular Ca²⁺ peaks and slowed Ca²⁺ removal, but not by increased markers of oxidative stress or impaired mitochondrial respiration.
2 context sentences(design, population, supporting numbers)
Summary · context
Cardiomyocyte contractile function was assessed in isolated cardiomyocytes by measuring sarcomere contractility, along with the determination of Ca²⁺ transient.
Summary · context
Male wild-type (WT) and knockout rats (4 months-old) were used.
In this study, L-carnosine was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking L-carnosine.
Report a problemFND-3403881407
12LabNot a test of L-carnosine aloneEx vivo tissueMechanism
In rat cardiomyocytes, CARNS1 knockout accompanied slower calcium removal.
In plain wordsIn lab tests, knockout rat heart cells removed calcium more slowly than wild-type cells.
Peptide
L-carnosine
Outcome
DecreaseCalcium removal
Study
ratn: not reported in source
CARNS1 knockout rats
Comparator
Wild-type rats
Outcome group
Heart function · Cardiovascular
Source sentences
Summary
Impaired systolic and diastolic dysfunction were accompanied by reduced intracellular Ca²⁺ peaks and slowed Ca²⁺ removal, but not by increased markers of oxidative stress or impaired mitochondrial respiration.
2 context sentences(design, population, supporting numbers)
Summary · context
Cardiomyocyte contractile function was assessed in isolated cardiomyocytes by measuring sarcomere contractility, along with the determination of Ca²⁺ transient.
Summary · context
Male wild-type (WT) and knockout rats (4 months-old) were used.
In this study, L-carnosine was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking L-carnosine.
Report a problemFND-3403881408

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
27 Oct 2026, 18:20 UTC
Study results updated
Version 1
27 Oct 2026, 16:32 UTC
First added · source update from Europe PMC

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