Effect on ex vivo platelet aggregation and in vivo cyclic flow with Na +/H+ exchange inhibition

Richard J. Gumina, Peter J. Newman, Garrett J. Gross

Research output: Contribution to journalArticle

Abstract

BIIB 513 and EMD 85131 are selective inhibitors of the Na +/H+ exchanger-1 (NHE-1) that are benzoylguanidine derivatives of the clinically employed diuretic amiloride. Prior studies have suggested a role for NHE-1 activity in platelet activation and aggregation using amiloride or its non- benzoylguanidines derivatives. However, the concentrations employed in these prior studies were at levels known to exert effects on other ion transport systems besides the NHE-1. Therefore, the purpose of this study was to examine the effects of more selective NHE-1 inhibitors, BIIB 513 and EMD 85131, on platelet aggregation and in vivo cyclic flow following arterial injury. BIIB 513 and EMD 85131 effects on ex vivo canine and human platelet aggregation in response to various agents was monitored via platelet aggregation. For analysis of in vivo thrombus formation, a femoral artery crush injury model was employed and a flow meter was used to monitor the effect of BIIB 513 on cyclic blood flow. Treatment of either canine or human platelets with up to 1 mM of BIIB 513 had no effect on aggregation induced by platelet activating factor (PAF), thrombin receptor activator peptide (TRAP), or adenosine diphosphate (ADP). Additionally, the structurally related compound EMD 85131 at up to 1 mM failed to inhibit TRAP induced platelet aggregation. In vivo administration of up to 9 mg/kg of BIIB 513 intravenously failed to affect cyclic flow in a canine model of femoral artery injury. These data demonstrate that the specific and selective NHE-1 inhibitors BIIB 513 or EMD 85131 have no effect on ex vivo platelet aggregation orin vivo cyclic flow following arterial injury.

Original languageEnglish (US)
Pages (from-to)431-435
Number of pages5
JournalJournal of Thrombosis and Thrombolysis
Volume31
Issue number4
DOIs
StatePublished - May 1 2011

Fingerprint

Platelet Aggregation
Sodium-Hydrogen Antiporter
Thrombin Receptors
Canidae
Amiloride
Femoral Artery
Wounds and Injuries
Ion Transport
Platelet Activation
BIIB 513
Diuretics
Adenosine Diphosphate
Thrombosis
Blood Platelets
hydrochloride N-diaminomethylene-2-methyl-5-methylsulfonyl-4-pyrrolobenzamide

Keywords

  • Animal model
  • Arterial thrombosis
  • Blood flow
  • Human
  • Platelet aggregation
  • Sodium-hydrogen exchanger

ASJC Scopus subject areas

  • Hematology
  • Cardiology and Cardiovascular Medicine

Cite this

Effect on ex vivo platelet aggregation and in vivo cyclic flow with Na +/H+ exchange inhibition. / Gumina, Richard J.; Newman, Peter J.; Gross, Garrett J.

In: Journal of Thrombosis and Thrombolysis, Vol. 31, No. 4, 01.05.2011, p. 431-435.

Research output: Contribution to journalArticle

Gumina, Richard J. ; Newman, Peter J. ; Gross, Garrett J. / Effect on ex vivo platelet aggregation and in vivo cyclic flow with Na +/H+ exchange inhibition. In: Journal of Thrombosis and Thrombolysis. 2011 ; Vol. 31, No. 4. pp. 431-435.
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