ArticleProceedings of the National Academy of Sciences of the United States of America2002
cAMP facilitates EDHF-type relaxations in conduit arteries by enhancing electrotonic conduction via gap junctions.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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.
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.
Who cites it
44 citing papers in PubMed, 122 citations in OpenAlex.
- Pathophysiology and Outcomes of Endothelium Function in Coronary Microvascular Diseases: A Systematic Review of Randomized Controlled Trials and Multicenter Study.Biomedicines · 2022Review
- Potentiation of Acetylcholine-Induced Relaxation of Aorta in Male UC Davis Type 2 Diabetes Mellitus (UCD-T2DM) Rats: Sex-Specific Responses.Frontiers in physiology · 2021Article
- Adenosine kinase inhibition enhances microvascular dilator function and improves left ventricle diastolic dysfunction.Microcirculation (New York, N.Y. : 1994) · 2020Article
- Endothelium-Derived Hyperpolarizing Factor and Myoendothelial Coupling: TheFrontiers in physiology · 2020Review
- Regulation of vascular tone by transient receptor potential ankyrin 1 channels.Current topics in membranes · 2020Review
- Interactions between renal vascular resistance and endothelium-derived hyperpolarization in hypertensive rats in vivo.Physiological reports · 2019Article
- Endothelium-Dependent Hyperpolarization (EDH) in Diabetes: Mechanistic Insights and Therapeutic Implications.International journal of molecular sciences · 2019Review
- Acid-base regulation and sensing: Accelerators and brakes in metabolic regulation of cerebrovascular tone.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2018Review
- Endothelium-Derived Hyperpolarization and Coronary Vasodilation: Diverse and Integrated Roles of Epoxyeicosatrienoic Acids, Hydrogen Peroxide, and Gap Junctions.Microcirculation (New York, N.Y. : 1994) · 2016Review
- Role of connexins and pannexins in cardiovascular physiology.Cellular and molecular life sciences : CMLS · 2015Review
- P2Y₂ receptor activation decreases blood pressure via intermediate conductance potassium channels and connexin 37.Acta physiologica (Oxford, England) · 2015Article
- Traumatic brain injury in vivo and in vitro contributes to cerebral vascular dysfunction through impaired gap junction communication between vascular smooth muscle cells.Journal of neurotrauma · 2014Article
- Endothelial control of vasodilation: integration of myoendothelial microdomain signalling and modulation by epoxyeicosatrienoic acids.Pflugers Archiv : European journal of physiology · 2014Review
- Exchange protein activated by cAMP (Epac) induces vascular relaxation by activating Ca2+-sensitive K+ channels in rat mesenteric artery.The Journal of physiology · 2013Article
- Activation of KCa3.1 by SKA-31 induces arteriolar dilatation and lowers blood pressure in normo- and hypertensive connexin40-deficient mice.British journal of pharmacology · 2013Article
- Endothelial alkalinisation inhibits gap junction communication and endothelium-derived hyperpolarisations in mouse mesenteric arteries.The Journal of physiology · 2013Article
- TRPA1 channels in the vasculature.British journal of pharmacology · 2012Review
- Regulator of G protein signaling 2 deficiency causes endothelial dysfunction and impaired endothelium-derived hyperpolarizing factor-mediated relaxation by dysregulating Gi/o signaling.The Journal of biological chemistry · 2012Article
- Cyclic nucleotide-dependent relaxation pathways in vascular smooth muscle.Cellular and molecular life sciences : CMLS · 2012Review
- Effects of connexin-mimetic peptides on perfusion pressure in response to phenylephrine in isolated, perfused rat kidneys.Clinical and experimental nephrology · 2011Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We have investigated the role of cAMP in NO- and prostanoid-independent relaxations that are widely attributed to an endothelium-derived hyperpolarizing factor (EDHF). Under control conditions EDHF-type relaxations evoked by acetylcholine (ACh) in rabbit iliac arteries were transient, but in the presence of the cAMP phosphodiesterase inhibitor isobutylmethylxanthine (IBMX) or the cell permeant cAMP analog 8-bromo-cAMP, relaxations became sustained with their maxima potentiated approximately 2-fold. Relaxation was associated with transient approximately 1.5-fold elevations in smooth muscle cAMP levels with both mechanical and nucleotide responses being abolished by interrupting gap junctional communication with the connexin-mimetic peptide Gap 27 and by endothelial denudation. However, IBMX induced a sustained endothelium-independent approximately 2-fold rise in cAMP levels, which was not further amplified by ACh, suggesting that the contribution of cAMP to the EDHF phenomenon is permissive. After selective loading of the endothelium with calcein AM, direct transfer of dye from the endothelium to the media was enhanced by IBMX or 8-bromo-cAMP, but not by 8-bromo-cGMP, whereas Gap 27 promoted sequestration within the intima. ACh-induced hyperpolarizations of subintimal smooth muscle in arterial strips with intact endothelium were abolished by Gap 27 and the adenylyl cyclase inhibitor 2',5'-dideoxyadenosine but were unaffected by IBMX. By contrast, in strips partially denuded of endothelium, IBMX enhanced the transmission of hyperpolarization from the endothelium to remote smooth muscle cells. These findings support the hypothesis that endothelial hyperpolarization underpins the EDHF phenomenon, with cAMP governing subsequent electrotonic signaling via both myoendothelial and homocellular smooth muscle gap junctions.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.