Evidence map›Paper›PMID 33836171›Full record

ArticleKidney international2021

A small molecule inhibitor of the chloride channel TMEM16A blocks vascular smooth muscle contraction and lowers blood pressure in spontaneously hypertensive rats.

Onur Cil, Xiaolan Chen, Henry R Askew Page, Samuel N Baldwin, Maria C Jordan, Pyone Myat Thwe, Marc O Anderson, Peter M Haggie, Iain A Greenwood, Kenneth P Roos and 1 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Kidney international, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
3.4field-weighted citation impact, top 7% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

24 citing papers in PubMed, 41 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Review
  5. The machinery of healthy vasodilatation: an overview.Pflugers Archiv : European journal of physiology · 2025
    Review
  6. Article
  7. Review
  8. Article
  9. Review
  10. Review
  11. Review
  12. Review
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors at 4 institutions in 2 countries.

Onur CilDepartment of Pediatrics, University of California, San Francisco, San Francisco, California, USA. Electronic address: onur.cil@ucsf.edu.
Xiaolan ChenDepartment of Medicine, University of California, San Francisco, San Francisco, California, USA; Department of Physiology, University of California, San Francisco, San Francisco, California, USA.
Henry R Askew PageVascular Biology Research Centre, Institute of Molecular and Clinical Sciences, St. George's University of London, London, UK.
Samuel N BaldwinVascular Biology Research Centre, Institute of Molecular and Clinical Sciences, St. George's University of London, London, UK.
Maria C JordanDepartment of Physiology, University of California, Los Angeles, Los Angeles, California, USA.
Pyone Myat ThweDepartment of Chemistry and Biochemistry, San Francisco State University, San Francisco, California, USA.
Marc O AndersonDepartment of Chemistry and Biochemistry, San Francisco State University, San Francisco, California, USA.
Peter M HaggieDepartment of Medicine, University of California, San Francisco, San Francisco, California, USA; Department of Physiology, University of California, San Francisco, San Francisco, California, USA.
Iain A GreenwoodVascular Biology Research Centre, Institute of Molecular and Clinical Sciences, St. George's University of London, London, UK.
Kenneth P RoosDepartment of Physiology, University of California, Los Angeles, Los Angeles, California, USA.
Alan S VerkmanDepartment of Medicine, University of California, San Francisco, San Francisco, California, USA; Department of Physiology, University of California, San Francisco, San Francisco, California, USA.
University of California, San Francisco · USSt George's, University of London · GBSan Francisco State University · USUniversity of California, Los Angeles · US

Funding

SynthesisP30DK072517 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI VERKMAN, ALAN S · 2005 to 2022
$18.1M
Functional Role of Aquaporins in Eye PhysiologyR01EY013574 · NEI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI VERKMAN, ALAN S · 2002 to 2022
$7.6M
SLC26A3 (DRA) Inhibitors for Treatment of Hyperoxaluria and NephrolithiasisR01DK126070 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CIL, ONUR · 2020 to 2024
$1.6M
British Heart Foundation FS/18/41/33762NEI NIH HHS R01 EY013574NIDDK NIH HHS P30 DK072517NIDDK NIH HHS R01 DK126070
6 · The paper itself

Abstract

Hypertension is a major cause of cardiovascular morbidity and mortality, despite the availability of antihypertensive drugs with different targets and mechanisms of action. Here, we provide evidence that pharmacological inhibition of TMEM16A (ANO1), a calcium-activated chloride channel expressed in vascular smooth muscle cells, blocks calcium-activated chloride currents and contraction in vascular smooth muscle in vitro and decreases blood pressure in spontaneously hypertensive rats. The acylaminocycloalkylthiophene TMinh-23 fully inhibited calcium-activated TMEM16A chloride current with nanomolar potency in Fischer rat thyroid cells expressing TMEM16A, and in primary cultures of rat vascular smooth muscle cells. TMinh-23 reduced vasoconstriction caused by the thromboxane mimetic U46619 in mesenteric resistance arteries of wild-type and spontaneously hypertensive rats, with a greater inhibition in spontaneously hypertensive rats. Blood pressure measurements by tail-cuff and telemetry showed up to a 45-mmHg reduction in systolic blood pressure lasting for four-six hours in spontaneously hypertensive rats after a single dose of TMinh-23. A minimal effect on blood pressure was seen in wild-type rats or mice treated with TMinh-23. Five-day twice daily treatment of spontaneously hypertensive rats with TMinh-23 produced sustained reductions of 20-25 mmHg in daily mean systolic and diastolic blood pressure. TMinh-23 action was reversible, with blood pressure returning to baseline in spontaneously hypertensive rats by three days after treatment discontinuation. Thus, our studies provide validation for TMEM16A as a target for antihypertensive therapy and demonstrate the efficacy of TMinh-23 as an antihypertensive with a novel mechanism of action.

Indexed as

HypertensionMuscle, Smooth, VascularVasoconstrictionAnimalsAnoctamin-1Blood PressureChloride ChannelsMuscle ContractionRatsRats, Inbred SHRANO1 protein, ratAnoctamin-1Chloride Channelsantihypertensiveshypertensionvasodilators

Identifiers

PMID33836171
PMCPMC8319106
OpenAlexW3148687971

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.