What does this research mean for the field?

Relaxation induced by K(ATP)-channel openers in rabbit coronary small arteries is mediated by K(ATP) channels and modulated by Na,K-pump activity. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

What question did this study set out to answer?

To evaluate the role of the Na,K-pump in arterial relaxations induced by KATP-channel openers in rabbit coronary small arteries.

November 24, 2004British Journal of PharmacologyOpen Access

KATP‐channel‐induced vasodilation is modulated by the Na,K‐pump activity in rabbit coronary small arteries

Q: What is the clinical evidence from this study?

Study design: Other. Intervention: K(ATP)-channel openers (pinacidil and cromakalim) vs. Inhibitors (glibenclamide, ouabain). Primary outcome: Arterial relaxation and K(ATP)-channel currents.

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Key result

Cromakalim and pinacidil relax rabbit coronary arteries via KATP channel opening modulated by Na,K-pump activity.

Population

Rabbit coronary small arteries and isolated smooth muscle cells from these arteries

Comparison

K-channel openers with or without Na,K-pump… vs Control conditions

Design

Preclinical

Authors

MGMarianne Glavind‐KristensenAarhus University Hospital VMVladimir V. MatchkovAarhus University VHVibeke HansenVejle Sygehus

Discussion

Member takes

Implication

Does not support clinical use of K(ATP) openers; leaves open Na,K-pump modulation of coronary vasoregulation in humans.

Key Points

To evaluate the role of the Na,K-pump in arterial relaxations induced by KATP-channel openers in rabbit coronary small arteries.
Mounted rabbit coronary small artery segments in myographs to record isometric tension during preconstriction with U46619 or high potassium (124 mM).
Assessed concentration-dependent relaxations to pinacidil and cromakalim in the presence of inhibitors such as ouabain, glibenclamide, and L-NNA, as well as endothelium removal.
Used whole-cell patch clamp electrophysiology to measure KATP-channel currents in isolated vascular smooth muscle cells with varying pipette sodium concentrations.
Pinacidil and cromakalim induced concentration-dependent relaxations in U46619-preconstricted arteries that were partly inhibited by 1 µM ouabain or potassium-free media, with cromakalim relaxations further inhibited by 1 µM glibenclamide.
Ouabain (1 µM) and glibenclamide (1 µM) each partly inhibited ATP-sensitive currents elicited by pinacidil and cromakalim, with additive inhibitory effects observed during co-administration.
Removing sodium from the patch pipette solution reduced the KATP current and completely abolished the inhibitory effect of ouabain.

Structured PICO

Population

Rabbit coronary small arteries and isolated smooth muscle cells from these arteries

Intervention

K(ATP)-channel openers (pinacidil and cromakalim) with or without Na,K-pump inhibition (ouabain) or K(ATP) channel blockade (glibenclamide)

Comparator

Control conditions (e.g., without inhibitors, potassium-free media, sodium-free pipette solution)

Outcome

Isometric tension (relaxation) and K(ATP)-channel currentssurrogate

Inhibition of the Na,K-pump modulates K(ATP)-channel-induced vasodilation in rabbit coronary arteries, likely by altering the local environment for K(ATP) channels.

Cite This Study

Glavind‐Kristensen et al. (2004) studied this question. K(ATP)-channel openers (pinacidil and cromakalim) vs. Inhibitors (glibenclamide, ouabain) was evaluated on Arterial relaxation and K(ATP)-channel currents. Relaxation to cromakalim and pinacidil in rabbit coronary small arteries is mediated through opening of K(ATP) channels, which is modulated by Na,K-pump activity.

synapsesocial.com/papers/6aa6a47e041e43fea73a7f39 https://doi.org/10.1038/sj.bjp.0706016

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KATP‐channel‐induced vasodilation is modulated by the Na,K‐pump activity in rabbit coronary small arteries

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

KATP‐channel‐induced vasodilation is modulated by the Na,K‐pump activity in rabbit coronary small arteries

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

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