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Study · Animal study (in vivo) · rat · 2017

3 results

Lack of Effects of Metformin and AICAR Chronic Infusion on the Development of Hypertension in Dahl Salt-Sensitive Rats.

Pavlov TS, Levchenko V, Ilatovskaya DV, Li H, Palygin O, Pastor-Soler NM, Hallows KR, Staruschenko A

Frontiers in physiology20 Apr 2017Cited by 20 (Europe PMC)

PMID28473772 (opens in a new tab)PMCIDPMC5397526 (opens in a new tab)DOI10.3389/fphys.2017.00227 (opens in a new tab)PepBankPUB-28473772
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Summary

In the kidney, reabsorption via the epithelial sodium channel (ENaC) is involved in long-term blood pressure control. Previously we demonstrated that ENaC hyperactivity is associated with development of salt-sensitive (SS) hypertension in Dahl SS rats. AMP-activated kinase (AMPK), playing a role in cellular energy homeostasis, has been shown to decrease ENaC activity. Here, we tested whether metformin and AICAR, two drugs that activate AMPK, affect the development of salt-induced hypertension. High salt diet significantly increased mean arterial pressure (MAP) in Dahl SS rats. Blood pressure elevation was accompanied by a short-term decline of heart rate and increased circadian arterial pressure dipping. Metformin and AICAR were delivered intravenously at doses of 200 and 20 mg/kg/day, respectively. However, both control and drug-treated groups had similar development of high blood pressure within 3 weeks of 8% NaCl dietary salt intake. In the metformin-treated animals MAP reached 164.9 ± 9.1 mmHg, which was not significantly different from the control group (171.8 ± 5.6 mmHg). Patch clamp analysis revealed that the metformin-treated rats had no difference in the activity of ENaC. AICAR treatment also did not affect the development of hypertension and kidney injury. MAP reached 182.8 ± 4.8 and 178.0 ± 2.8 mmHg in AICAR and vehicle treated groups, respectively. Of note, we found that high-salt diet activated AMPK in the Dahl SS rats, and treatment with these AMPK activators had no significant further effect on AMPK activity. We conclude that AMPK activators, at least under these conditions, do not affect development of hypertension during high-salt diet in the Dahl SS rat model.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study3

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

  1. 01AnimalAnimal study (in vivo)Efficacy outcome

    In Dahl salt-sensitive rats, AICAR did not affect hypertension development compared with vehicle.

    In plain wordsIn rats, AICAR did not change high blood pressure development compared with vehicle.

    Peptide
    AICAR (acadesine)
    Outcome
    No significant changeMean arterial pressure
    Study

    ratn: not reported in source

    Dahl salt-sensitive rats on high-salt diet
    Comparator
    vehicle
    Outcome group
    Blood pressure · Cardiovascular
    Studied dose
    20 mg/kg/day · intravenous · 3 weeksAs given in this study (rat).

    Measurements

    MAP
    182.8 mmHg
    AICAR
    MAP
    178 mmHg
    vehicle

    Source sentences

    Summary
    MAP reached 182.8 ± 4.8 and 178.0 ± 2.8 mmHg in AICAR and vehicle treated groups, respectively.
    3 context sentences
    Summary · context
    AICAR treatment also did not affect the development of hypertension and kidney injury.
    Summary · context
    However, both control and drug-treated groups had similar development of high blood pressure within 3 weeks of 8% NaCl dietary salt intake.
    Summary · context
    Metformin and AICAR were delivered intravenously at doses of 200 and 20 mg/kg/day, respectively.
  2. 02AnimalAnimal study (in vivo)Efficacy outcome

    In Dahl salt-sensitive rats, AICAR did not affect kidney injury.

    In plain wordsIn rats, AICAR did not change kidney injury compared with vehicle.

    Peptide
    AICAR (acadesine)
    Outcome
    No significant changeKidney injury
    Study

    ratn: not reported in source

    Dahl salt-sensitive rats on high-salt diet
    Comparator
    vehicle
    Outcome group
    Kidney function · Kidney and urinary
    Studied dose
    20 mg/kg/day · intravenous · 3 weeksAs given in this study (rat).

    Source sentences

    Summary
    AICAR treatment also did not affect the development of hypertension and kidney injury.
    1 context sentence
    Summary · context
    Metformin and AICAR were delivered intravenously at doses of 200 and 20 mg/kg/day, respectively.

Studies that did not test the peptide alone1

In this study, AICAR (acadesine) 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 AICAR (acadesine).

  1. 03AnimalNot a test of AICAR (acadesine) aloneAnimal study (in vivo)Mechanism

    In high-salt-fed Dahl rats, pooled AMPK activator treatments caused no significant additional effect on AMPK activity.

    In plain wordsIn rats, AMPK activators including AICAR did not further change AMPK activity during high-salt feeding.

    Peptide
    AICAR (acadesine)
    Outcome
    No significant changeAMPK activity
    Study

    ratn: not reported in source

    Dahl salt-sensitive rats on high-salt diet
    Comparator
    vehicle
    Outcome group
    Receptor activity and mechanism · Cardiovascular

    Source sentences

    Summary
    Of note, we found that high-salt diet activated AMPK in the Dahl SS rats, and treatment with these AMPK activators had no significant further effect on AMPK activity.
    1 context sentence
    Summary · context
    Metformin and AICAR were delivered intravenously at doses of 200 and 20 mg/kg/day, respectively.

    In this study, AICAR (acadesine) 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 AICAR (acadesine).

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.

  1. Version 2Current

    21 Oct 2026, 15:58 UTC

    Study results updated

  2. Version 1

    21 Oct 2026, 12:50 UTC

    First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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