Evidence map›Paper›PMID 39189991›Full record

ArticleAmerican journal of hypertension2024

The KCa3.1 Channel Blocker TRAM-34 and Minocycline Prevent Fructose-Induced Hypertension in Rats.

Abdelrahman Hamad, Melike Hacer Ozkan

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Article in American journal of hypertension, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

2 authors.

Abdelrahman HamadDepartment of Pharmacology, Faculty of Pharmacy, Hacettepe University, Ankara, Turkiye.ORCID 0000-0002-0470-9995
Melike Hacer OzkanDepartment of Pharmacology, Faculty of Pharmacy, Hacettepe University, Ankara, Turkiye.ORCID 0000-0003-1339-2616

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundHigh fructose consumption increases blood pressure through microglia-related neuroinflammation in rats. Since intermediate-conductance calcium-activated potassium channels (KCa3.1) potentiates microglial reactivity, we examined whether the pretreatment with the KCa3.1 channel blocker TRAM-34 or minocycline prevents hypertension development in fructose-fed rats.

methodsThe study involved male Wistar rats that were given either high fructose (10% in drinking water) or tap water for 21 days. Fructose groups also received minocycline or TRAM-34 systemically for 21 days. We measured systolic and diastolic blood pressure (SBP and DBP), heart rate (HR) periodically with tail-cuff; proinflammatory cytokines, and insulin levels in plasma via Enzyme-linked immunosorbent assay (ELISA), and neuroinflammatory markers in the nucleus tractus solitarii (NTS) by qPCR at the end of 21 days. We also examined endothelium-dependent hyperpolarization (EDH)-type vasorelaxations in isolated mesenteric arteries of the rats ex vivo.

resultsSBP, DBP, and HR increased in the fructose group. Both minocycline and TRAM-34 significantly prevented these increases. Fructose intake also increased plasma interleukin-6, interleukin-1β, tumor necrosis factor-α, and insulin levels, whereas pretreatment with TRAM-34 prevented these increases as well. Iba-1, but not cluster of differentiation-86 levels were significantly higher in the NTS samples of fructose-fed hypertensive rats which implied microglial proliferation. EDH-type vasorelaxations mediated by endothelial KCa3.1 attenuated in the fructose group; however, TRAM-34 did not cause further deterioration in the relaxations.

conclusionsTRAM-34 is as effective as minocycline in preventing fructose-induced hypertension without interfering with EDH-type vasodilation. Furthermore, TRAM-34 relieves high fructose-associated systemic inflammation.

Indexed as

Blood PressureFructoseHypertensionIntermediate-Conductance Calcium-Activated Potassium ChannelsMinocyclinePyrazolesRats, WistarVasodilationAnimalsCytokinesDisease Models, AnimalInflammation MediatorsInsulinMaleMesenteric ArteriesMicrogliaCytokinesFructoseInflammation MediatorsInsulinIntermediate-Conductance Calcium-Activated Potassium ChannelsKcnn4 protein, ratMinocyclinePotassium Channel BlockersPyrazolesTRAM 34blood pressurefructosehypertensionminocyclineratTRAM-34

Identifiers

PMID39189991
PMCPMC11664185

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.