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Small and Intermediate Calcium-Activated Potassium Channel Openers Improve Rat Endothelial and Erectile Function

Overview of attention for article published in Frontiers in Pharmacology, September 2017
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Title
Small and Intermediate Calcium-Activated Potassium Channel Openers Improve Rat Endothelial and Erectile Function
Published in
Frontiers in Pharmacology, September 2017
DOI 10.3389/fphar.2017.00660
Pubmed ID
Authors

Simon G. Comerma-Steffensen, Ingrid Carvacho, Elise R. Hedegaard, Ulf Simonsen

Abstract

Modulation of endothelial calcium-activated potassium (KCa) channels has been proposed as an approach to restore endothelial function. The present study investigated whether novel openers of KCa channels with small (KCa2.x) and intermediate (KCa3.1) conductance, NS309 and NS4591, improve endothelium-dependent relaxation and erectile function. Rat corpus cavernosum (CC) strips were mounted for isometric tension recording and processed for immunoblotting. Mean arterial pressure (MAP), intracavernosal pressure (ICP), and electrocardiographic (ECG) measurements were conducted in anesthetized rats. Immunoblotting revealed the presence of KCa2.3 and large KCa conductance (KCa1.1) channels in the corpus cavernosum. NS309 and NS4591 increased current in CC endothelial cells in whole cell patch clamp experiments. Relaxation induced by NS309 (<1 μM) was inhibited by endothelial cell removal and high extracellular potassium. An inhibitor of nitric oxide (NO) synthase, and blockers of KCa2.x and KCa1.1 channels, apamin and iberiotoxin also inhibited NS309 relaxation. Incubation with NS309 (0.5 μM) markedly enhanced acetylcholine relaxation. Basal erectile function (ICP/MAP) increased during administration of NS309. Increases in ICP/MAP after cavernous nerve stimulation with NS309 were unchanged, whereas NS4591 significantly improved erectile function. Administration of NS309 and NS4591 caused small changes in the electrocardiogram, but neither arrhythmic events nor prolongation of the QTc interval were observed. The present study suggests that openers of KCa2.x and KCa3.1 channels improve endothelial and erectile function. The effects of NS309 and NS4591 on heart rate and ECG are small, but will require additional safety studies before evaluating whether activation of KCa2.3 channels has a potential for treatment of erectile dysfunction.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 14 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 14 100%

Demographic breakdown

Readers by professional status Count As %
Lecturer 2 14%
Researcher 2 14%
Student > Postgraduate 2 14%
Student > Master 2 14%
Student > Bachelor 1 7%
Other 3 21%
Unknown 2 14%
Readers by discipline Count As %
Agricultural and Biological Sciences 3 21%
Medicine and Dentistry 3 21%
Nursing and Health Professions 1 7%
Business, Management and Accounting 1 7%
Chemistry 1 7%
Other 0 0%
Unknown 5 36%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 21 September 2017.
All research outputs
#14,955,443
of 23,002,898 outputs
Outputs from Frontiers in Pharmacology
#5,285
of 16,309 outputs
Outputs of similar age
#188,495
of 318,397 outputs
Outputs of similar age from Frontiers in Pharmacology
#88
of 275 outputs
Altmetric has tracked 23,002,898 research outputs across all sources so far. This one is in the 32nd percentile – i.e., 32% of other outputs scored the same or lower than it.
So far Altmetric has tracked 16,309 research outputs from this source. They receive a mean Attention Score of 5.0. This one has gotten more attention than average, scoring higher than 60% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 318,397 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 37th percentile – i.e., 37% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 275 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 62% of its contemporaries.