A role for potassium channels in smooth muscle cells and platelets in the etiology of primary pulmonary hypertension.

@article{Weir1998ARF,
  title={A role for potassium channels in smooth muscle cells and platelets in the etiology of primary pulmonary hypertension.},
  author={Edward Kenneth Weir and Helen L. Reeve and Gerhard Johnson and Evangelos D. Michelakis and Daniel P. Nelson and Stephen L. Archer},
  journal={Chest},
  year={1998},
  volume={114 3 Suppl},
  pages={
          200S-204S
        }
}
Plasma serotonin levels are markedly elevated in patients with primary pulmonary hypertension (PPH) and platelet levels of serotonin are low. Furthermore, plasma serotonin levels remain elevated after bilateral lung transplantation, in the absence of any pulmonary hypertension. Dexfenfluramine can cause the anorexigen-induced form of PPH that is clinically and histologically indistinguishable from PPH. We find that dexfenfluramine releases serotonin from platelets and inhibits its reuptake… 
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α1-Adrenergic Hypothesis for Pulmonary Hypertension
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A further understanding of theα 1 -adrenoreceptor subtypes present in the pulmonary vasculature, the factors that regulate their expression, and their intracellular signaling pathways would help researchers to devise newer therapeutic strategies and, hopefully, to find a cure for this crippling condition.
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Although there is not a generally accepted, unifying hypothesis regarding its cause, impaired function and the expression of vascular and platelet Kv channels suggest PPH may be a disease of the ion channels.
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TLDR
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TLDR
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Stephen Archer and Stuart Rich ' ' Work in Progress ' ' Primary Pulmonary Hypertension : A Vascular Biology and Translational Research
TLDR
Impaired function and the expression of vascular and platelet Kv channels suggest PPH may be a disease of the ion channels, which could explain the abnormal vascular tone, platelet activation, and remodeling in PPH.
Anorectic drugs and vascular disease: the role of voltage-gated K+ channels.
Anorectic drugs and pulmonary hypertension from the bedside to the bench.
TLDR
One potentially beneficial effect of the epidemics of anorectic-related PPH is that it may have provided important insights into the causes of PPH unrelated to anorexia, as evidence suggests that potassium channel abnormalities and vasoactive and proliferative properties of 5-HT may play a role.
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TLDR
Treatment with MCI-9042 significantly inhibited the development of MCT-PH along with a decrease in the number of PCNA-positive cells, suggesting a pivotal role of serotonin in the developmentof PH induced by MCT.
Fenfluramine-induced pulmonary vasoconstriction: role of serotonin receptors and potassium channels.
TLDR
The data indicate that the pulmonary vasoconstrictor response to fenfluramine is partly mediated by 5-HT receptors, and suggests that preexisting K(V)-channel insufficiency may predispose some patients to the development of pulmonary hypertension during fen fluramine treatment.
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TLDR
chamitriptyline (AMI), iprindole and imipramine caused dose-dependent prolonged rises in pulmonary artery pressure and oedema in anaesthetised cats in vivo, and chronic AMI led to attenuation of the pressor action of 5‐HT, especially when associated with chronic hypoxic-induced pulmonary hypertension.
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References

SHOWING 1-10 OF 38 REFERENCES
Direct role for potassium channel inhibition in hypoxic pulmonary vasoconstriction.
TLDR
Results indicate that K+ channel inhibition may be a key event that links hypoxia to pulmonary vasoconstriction by causing membrane depolarization and subsequent Ca2+ entry.
Increased plasma serotonin in primary pulmonary hypertension.
The mechanism of acute hypoxic pulmonary vasoconstriction: the tale of two channels
  • E. K. Weir, S. Archer
  • Biology, Medicine
    FASEB journal : official publication of the Federation of American Societies for Experimental Biology
  • 1995
TLDR
There is evidence to suggest that changes in the redox status of the oxygen‐sensitive potassium channel or channels may control current flow, so that the channel is open when oxidized and closed when reduced.
Anorexic agents aminorex, fenfluramine, and dexfenfluramine inhibit potassium current in rat pulmonary vascular smooth muscle and cause pulmonary vasoconstriction.
TLDR
Observations indicate that anorexic agents, like hypoxia, can inhibit potassium current, cause membrane depolarization, and stimulate pulmonary vasoconstriction, and suggest one mechanism that could be responsible for initiating pulmonary hypertension in susceptible individuals.
Paradoxical constriction to platelets by arteries from rats with pulmonary hypertension.
TLDR
PAs from FHR with spontaneous pulmonary hypertension exhibit paradoxical constriction to both normal and storage pool deficient platelets.
Aggregating platelets contract isolated canine pulmonary arteries by releasing 5-hydroxytryptamine.
TLDR
Five experiments demonstrate that in the canine pulmonary artery 5-hydroxytryptamine is the predominant mediator of the contractile response triggered by platelet aggregation; and unlike in other blood vessels, the endothelium cannot curtail the contractiles response to aggregating platelets.
Serotonin produces both hyperplasia and hypertrophy of bovine pulmonary artery smooth muscle cells in culture.
TLDR
It is shown that 5-HT causes proliferation of both pulmonary artery and aortic SMC but not of endothelial cells or fibroblasts, and c-myc and alpha- and beta-actin gene expressions of pulmonary artery SMC were elevated after 2-h incubation with 5- HT, before stimulation of [3H]thymidine incorporation.
Differential distribution of electrophysiologically distinct myocytes in conduit and resistance arteries determines their response to nitric oxide and hypoxia.
TLDR
It is concluded that regional electrophysiological diversity among smooth muscle cells is a major determinant of segmental differences in vascular reactivity.
Hypoxia reduces potassium currents in cultured rat pulmonary but not mesenteric arterial myocytes.
TLDR
The hypoxia-induced inhibition of Iout in PA cells was accompanied by an apparent increase in inward Ca2+ current, and some of the channels responsible for this current may be open at the resting membrane potential of PA cells used in this study.
A new role for an old molecule: serotonin as a mitogen.
TLDR
Serotonin (5-hydroxytryptamine) has been known for the last half century to influence vasoactivity and to participate in neurotransmission and it has been proposed that, through these signaling pathways, serotonin plays an important role in remodeling of both the pulmonary and systemic circulations.
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