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pubmed-article:9461228pubmed:abstractTextWe report that a genetic polymorphism of the alpha2-adrenergic receptor (A2AR) encoded by chromosome 10 is associated with hypertension and an increase in epinephrine-mediated platelet aggregation in humans. The mechanism responsible for this heritable contrast in sensitivity to epinephrine is unknown. We tested our hypothesis that epinephrine-induced platelet aggregation is mediated by activation of chloride transport. We measured epinephrine-mediated increases in optical density of gel-filtered platelets suspended in a bicarbonate-buffered physiological salt solution. Compared with platelets incubated in the control buffer (130 mmol/L NaCl), platelets incubated with either bumetanide, a Na/K/2Cl cotransport inhibitor; anthracene-9-carboxylic acid, a chloride channel blocker; or acetazolamide, an agent that blocks ATP-dependent chloride transport had significantly decreased aggregation responses to epinephrine. When measured fluorometrically, epinephrine significantly increased intraplatelet chloride concentrations. Chloride-dependent modifications of epinephrine-induced platelet aggregation were not attributable to changes in A2AR ligand binding characteristics or to the concentration of platelet cAMP. Finally, subthreshold concentrations of epinephrine also potentiated thrombin-induced platelet aggregation, and blockade of chloride transport diminished this synergistic action of epinephrine on thrombin-stimulated platelet aggregation. Heritable differences in epinephrine-mediated platelet aggregation may be attributable to genetic differences in chloride transport in platelets. Furthermore, because we observed a necessary role for chloride transport in epinephrine-mediated platelet aggregation, pharmacological agents that block chloride transport, such as diuretics, may provide salutary protection against vascular thrombosis in patients with hypertension independent of the effect of these drugs on blood pressure.lld:pubmed
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pubmed-article:9461228pubmed:dateRevised2007-11-14lld:pubmed
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pubmed-article:9461228pubmed:year1998lld:pubmed
pubmed-article:9461228pubmed:articleTitleMechanism of epinephrine-induced platelet aggregation.lld:pubmed
pubmed-article:9461228pubmed:affiliationWayne State University School of Medicine, Veterans Administration Medical Center, Detroit, Mich 48201, USA.lld:pubmed
pubmed-article:9461228pubmed:publicationTypeJournal Articlelld:pubmed
pubmed-article:9461228pubmed:publicationTypeResearch Support, U.S. Gov't, P.H.S.lld:pubmed
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