Evidence map›Paper›PMID 24790136›Full record

ArticleArteriosclerosis, thrombosis, and vascular biology2014

Rap1b in smooth muscle and endothelium is required for maintenance of vascular tone and normal blood pressure.

Sribalaji Lakshmikanthan, Bartosz J Zieba, Zhi-Dong Ge, Ko Momotani, Xiaodong Zheng, Hayley Lund, Mykhaylo V Artamonov, Jason E Maas, Aniko Szabo, David X Zhang and 4 more

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

Article in Arteriosclerosis, thrombosis, and vascular biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed
3.3field-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

37 citing papers in PubMed, 54 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Divergent Functions of Rap1A and Rap1B in Endothelial Biology and Disease.International journal of molecular sciences · 2025
    Review
  5. Article
  6. Article
  7. A low androgen state impairs erectile function by suppressingTranslational andrology and urology · 2023
    Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Review
  18. EPAC in Vascular Smooth Muscle Cells.International journal of molecular sciences · 2020
    Review
  19. Integration of Rap1 and Calcium Signaling.International journal of molecular sciences · 2020
    Review
  20. Selective small-molecule EPAC activators.Biochemical Society transactions · 2019
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors at 2 institutions in 1 country.

Sribalaji LakshmikanthanFrom the Blood Research Institute, BloodCenter of Wisconsin, Milwaukee (S.L., M.C.W.); Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville (B.J.Z., K.M., M.V.A., A.V.S.); and Department of Pharmacology and Toxicology (Z.-D.G., J.A.A.), Cardiovascular Center (Z.-D.G., X.Z., J.E.M., D.X.Z., J.A.A.), Department of Medicine (X.Z., J.E.M., D.X.Z.), Department of Physiology (H.L., D.L.M.), and Division of Biostatistics (A.S.), Medical College of Wisconsin, Milwaukee.
Bartosz J ZiebaFrom the Blood Research Institute, BloodCenter of Wisconsin, Milwaukee (S.L., M.C.W.); Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville (B.J.Z., K.M., M.V.A., A.V.S.); and Department of Pharmacology and Toxicology (Z.-D.G., J.A.A.), Cardiovascular Center (Z.-D.G., X.Z., J.E.M., D.X.Z., J.A.A.), Department of Medicine (X.Z., J.E.M., D.X.Z.), Department of Physiology (H.L., D.L.M.), and Division of Biostatistics (A.S.), Medical College of Wisconsin, Milwaukee.
Zhi-Dong GeFrom the Blood Research Institute, BloodCenter of Wisconsin, Milwaukee (S.L., M.C.W.); Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville (B.J.Z., K.M., M.V.A., A.V.S.); and Department of Pharmacology and Toxicology (Z.-D.G., J.A.A.), Cardiovascular Center (Z.-D.G., X.Z., J.E.M., D.X.Z., J.A.A.), Department of Medicine (X.Z., J.E.M., D.X.Z.), Department of Physiology (H.L., D.L.M.), and Division of Biostatistics (A.S.), Medical College of Wisconsin, Milwaukee.
Ko MomotaniFrom the Blood Research Institute, BloodCenter of Wisconsin, Milwaukee (S.L., M.C.W.); Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville (B.J.Z., K.M., M.V.A., A.V.S.); and Department of Pharmacology and Toxicology (Z.-D.G., J.A.A.), Cardiovascular Center (Z.-D.G., X.Z., J.E.M., D.X.Z., J.A.A.), Department of Medicine (X.Z., J.E.M., D.X.Z.), Department of Physiology (H.L., D.L.M.), and Division of Biostatistics (A.S.), Medical College of Wisconsin, Milwaukee.
Xiaodong ZhengFrom the Blood Research Institute, BloodCenter of Wisconsin, Milwaukee (S.L., M.C.W.); Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville (B.J.Z., K.M., M.V.A., A.V.S.); and Department of Pharmacology and Toxicology (Z.-D.G., J.A.A.), Cardiovascular Center (Z.-D.G., X.Z., J.E.M., D.X.Z., J.A.A.), Department of Medicine (X.Z., J.E.M., D.X.Z.), Department of Physiology (H.L., D.L.M.), and Division of Biostatistics (A.S.), Medical College of Wisconsin, Milwaukee.
Hayley LundFrom the Blood Research Institute, BloodCenter of Wisconsin, Milwaukee (S.L., M.C.W.); Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville (B.J.Z., K.M., M.V.A., A.V.S.); and Department of Pharmacology and Toxicology (Z.-D.G., J.A.A.), Cardiovascular Center (Z.-D.G., X.Z., J.E.M., D.X.Z., J.A.A.), Department of Medicine (X.Z., J.E.M., D.X.Z.), Department of Physiology (H.L., D.L.M.), and Division of Biostatistics (A.S.), Medical College of Wisconsin, Milwaukee.
Mykhaylo V ArtamonovFrom the Blood Research Institute, BloodCenter of Wisconsin, Milwaukee (S.L., M.C.W.); Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville (B.J.Z., K.M., M.V.A., A.V.S.); and Department of Pharmacology and Toxicology (Z.-D.G., J.A.A.), Cardiovascular Center (Z.-D.G., X.Z., J.E.M., D.X.Z., J.A.A.), Department of Medicine (X.Z., J.E.M., D.X.Z.), Department of Physiology (H.L., D.L.M.), and Division of Biostatistics (A.S.), Medical College of Wisconsin, Milwaukee.
Jason E MaasFrom the Blood Research Institute, BloodCenter of Wisconsin, Milwaukee (S.L., M.C.W.); Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville (B.J.Z., K.M., M.V.A., A.V.S.); and Department of Pharmacology and Toxicology (Z.-D.G., J.A.A.), Cardiovascular Center (Z.-D.G., X.Z., J.E.M., D.X.Z., J.A.A.), Department of Medicine (X.Z., J.E.M., D.X.Z.), Department of Physiology (H.L., D.L.M.), and Division of Biostatistics (A.S.), Medical College of Wisconsin, Milwaukee.
Aniko SzaboFrom the Blood Research Institute, BloodCenter of Wisconsin, Milwaukee (S.L., M.C.W.); Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville (B.J.Z., K.M., M.V.A., A.V.S.); and Department of Pharmacology and Toxicology (Z.-D.G., J.A.A.), Cardiovascular Center (Z.-D.G., X.Z., J.E.M., D.X.Z., J.A.A.), Department of Medicine (X.Z., J.E.M., D.X.Z.), Department of Physiology (H.L., D.L.M.), and Division of Biostatistics (A.S.), Medical College of Wisconsin, Milwaukee.
David X ZhangFrom the Blood Research Institute, BloodCenter of Wisconsin, Milwaukee (S.L., M.C.W.); Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville (B.J.Z., K.M., M.V.A., A.V.S.); and Department of Pharmacology and Toxicology (Z.-D.G., J.A.A.), Cardiovascular Center (Z.-D.G., X.Z., J.E.M., D.X.Z., J.A.A.), Department of Medicine (X.Z., J.E.M., D.X.Z.), Department of Physiology (H.L., D.L.M.), and Division of Biostatistics (A.S.), Medical College of Wisconsin, Milwaukee.
John A AuchampachFrom the Blood Research Institute, BloodCenter of Wisconsin, Milwaukee (S.L., M.C.W.); Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville (B.J.Z., K.M., M.V.A., A.V.S.); and Department of Pharmacology and Toxicology (Z.-D.G., J.A.A.), Cardiovascular Center (Z.-D.G., X.Z., J.E.M., D.X.Z., J.A.A.), Department of Medicine (X.Z., J.E.M., D.X.Z.), Department of Physiology (H.L., D.L.M.), and Division of Biostatistics (A.S.), Medical College of Wisconsin, Milwaukee.
David L MattsonFrom the Blood Research Institute, BloodCenter of Wisconsin, Milwaukee (S.L., M.C.W.); Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville (B.J.Z., K.M., M.V.A., A.V.S.); and Department of Pharmacology and Toxicology (Z.-D.G., J.A.A.), Cardiovascular Center (Z.-D.G., X.Z., J.E.M., D.X.Z., J.A.A.), Department of Medicine (X.Z., J.E.M., D.X.Z.), Department of Physiology (H.L., D.L.M.), and Division of Biostatistics (A.S.), Medical College of Wisconsin, Milwaukee.
Avril V SomlyoFrom the Blood Research Institute, BloodCenter of Wisconsin, Milwaukee (S.L., M.C.W.); Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville (B.J.Z., K.M., M.V.A., A.V.S.); and Department of Pharmacology and Toxicology (Z.-D.G., J.A.A.), Cardiovascular Center (Z.-D.G., X.Z., J.E.M., D.X.Z., J.A.A.), Department of Medicine (X.Z., J.E.M., D.X.Z.), Department of Physiology (H.L., D.L.M.), and Division of Biostatistics (A.S.), Medical College of Wisconsin, Milwaukee.
Magdalena Chrzanowska-WodnickaFrom the Blood Research Institute, BloodCenter of Wisconsin, Milwaukee (S.L., M.C.W.); Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville (B.J.Z., K.M., M.V.A., A.V.S.); and Department of Pharmacology and Toxicology (Z.-D.G., J.A.A.), Cardiovascular Center (Z.-D.G., X.Z., J.E.M., D.X.Z., J.A.A.), Department of Medicine (X.Z., J.E.M., D.X.Z.), Department of Physiology (H.L., D.L.M.), and Division of Biostatistics (A.S.), Medical College of Wisconsin, Milwaukee. Magdalena.Wodnicka@bcw.edu.
Versiti Blood Center of Wisconsin · USUniversity of Virginia · US

Funding

VASOPRESSIN SECRETION AND CARDIOVASCULAR FUNCTIONP01HL029587 · NHLBI · MEDICAL COLLEGE OF WISCONSIN · PI ROMAN, RICHARD J. · 1985 to 2012
$24.1M
Role of GATA4 and GATA6 in Controlling Heart DevelopmentP01HL089471 · NHLBI · MEDICAL COLLEGE OF WISCONSIN · PI NORTH, PAULA E. · 2009 to 2013
$7.9M
TRP Channels In The Regulation of Vascular ToneR01HL096647 · NHLBI · MEDICAL COLLEGE OF WISCONSIN · PI ZHANG, DAVID X. · 2011 to 2024
$5.5M
Molecular Mechanisms of RhoA-mediated Ca2+Sensitization in Vascular Smooth MuscleR01GM086457 · NIGMS · UNIVERSITY OF VIRGINIA · PI DEREWENDA, URSZULA, DEREWENDA, ZYGMUNT S · 2009 to 2017
$5.4M
Role of Adenosine Receptors in Tissue ProtectionR01HL077707 · NHLBI · MEDICAL COLLEGE OF WISCONSIN · PI AUCHAMPACH, JOHN A · 2005 to 2014
$3.4M
Rap1 in VEGF signaling in endothelial cellsR01HL111582 · NHLBI · VERSITI WISCONSIN, INC. · PI CHRZANOWSKA, MAGDALENA · 2012 to 2019
$3.3M
EET-Induced Cardioprotection: Role of Opioids and Nitric Oxide (NO)R01HL111392 · NHLBI · MEDICAL COLLEGE OF WISCONSIN · PI AUCHAMPACH, JOHN A · 2012 to 2016
$2.2M
Role of CD247 in Salt-Sensitive Hypertension and Renal DiseaseR01DK096859 · NIDDK · MEDICAL COLLEGE OF WISCONSIN · PI MATTSON, DAVID L. · 2012 to 2016
$1.7M
Myosin phosphatase autoinhibition in gastrointestinal smooth muscle contractionR01DK088905 · NIDDK · UNIVERSITY OF VIRGINIA · PI ETO, MASUMI, SOMLYO, AVRIL V. · 2010 to 2012
$1.1M
MECHANISMS OF ALVEOLAR LIQUID &PROTEIN CLEARANCEF32HL007707 · NHLBI · UNIVERSITY OF CALIFORNIA SAN FRANCISCO · PI MASSA, LORRAINE GATES · 1987 to 1987
–
NHLBI NIH HHS HL07707NHLBI NIH HHS HL089471NHLBI NIH HHS HL096647NHLBI NIH HHS HL111583NHLBI NIH HHS HL29587NHLBI NIH HHS P01 HL029587NHLBI NIH HHS P01 HL089471NHLBI NIH HHS R01 HL077707NHLBI NIH HHS R01 HL096647NHLBI NIH HHS R01 HL111392NHLBI NIH HHS R01 HL111582NIDDK NIH HHS DK088905NIDDK NIH HHS DK96859NIDDK NIH HHS R01 DK088905NIDDK NIH HHS R01 DK096859NIGMS NIH HHS GM86457NIGMS NIH HHS R01 GM086457
6 · The paper itself

Abstract

objectiveSmall GTPase Ras-related protein 1 (Rap1b) controls several basic cellular phenomena, and its deletion in mice leads to several cardiovascular defects, including impaired adhesion of blood cells and defective angiogenesis. We found that Rap1b(-/-) mice develop cardiac hypertrophy and hypertension. Therefore, we examined the function of Rap1b in regulation of blood pressure. APPROACH AND

resultsRap1b(-/-) mice developed cardiac hypertrophy and elevated blood pressure, but maintained a normal heart rate. Correcting elevated blood pressure with losartan, an angiotensin II type 1 receptor antagonist, alleviated cardiac hypertrophy in Rap1b(-/-) mice, suggesting a possibility that cardiac hypertrophy develops secondary to hypertension. The indices of renal function and plasma renin activity were normal in Rap1b(-/-) mice. Ex vivo, we examined whether the effect of Rap1b deletion on smooth muscle-mediated vessel contraction and endothelium-dependent vessel dilation, 2 major mechanisms controlling basal vascular tone, was the basis for the hypertension. We found increased contractility on stimulation with a thromboxane analog or angiotensin II or phenylephrine along with increased inhibitory phosphorylation of myosin phosphatase under basal conditions consistent with elevated basal tone and the observed hypertension. Cyclic adenosine monophosphate-dependent relaxation in response to Rap1 activator, Epac, was decreased in vessels from Rap1b(-/-) mice. Defective endothelial release of dilatory nitric oxide in response to elevated blood flow leads to hypertension. We found that nitric oxide-dependent vasodilation was significantly inhibited in Rap1b-deficient vessels.

conclusionsThis is the first report to indicate that Rap1b in both smooth muscle and endothelium plays a key role in maintaining blood pressure by controlling normal vascular tone.

Indexed as

Blood PressureVasoconstrictionVasodilationAngiotensin II Type 1 Receptor BlockersAnimalsAntihypertensive AgentsCardiomegalyCells, CulturedDose-Response Relationship, DrugEndothelial CellsFemaleHumansHypertensionMaleMiceMice, KnockoutAngiotensin II Type 1 Receptor BlockersAntihypertensive AgentsNitric OxideNitric Oxide Synthase Type IIINOS3 protein, humanNos3 protein, mouseRAP1B protein, humanRap1b protein, mouserap GTP-Binding ProteinsVasoconstrictor AgentsVasodilator Agentsrelaxationsignal transductionvasodilation

Identifiers

PMID24790136
PMCPMC4224284
OpenAlexW2125744206

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Registered trials

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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.