Effect of Amine Metabolism by SSAO on Endothelium-Dependent Vasodilatory Responses of Krebs Perfused Equine Digits

Article Outline

• Introduction
• Materials & Methods
• Results
• Discussion
• Conclusion, Clinical Relevance & Take Home Message
• Copyright

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Introduction 

Increased amine production by the hind gut is thought to be implicated in the pathogenesis of equine laminitis. Semicarbazide-sensitive amine oxidase (SSAO) is an enzyme that belongs to copper-containing amine oxidases which catalyse the oxidative deamination of primary amines. Increased SSAO activity is thought to play a role in endothelial dysfunction and seasonal increases in plasma SSAO have been documented.

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Materials & Methods 

Hind limbs were obtained from mixed breed, healthy adult horses euthanased at an abattoir (n = 4-6), for reasons other than research, and were perfused with modified Krebs-Henseleit solution. Vasodilatory responses to bolus doses of carbachol (CCh) and sodium nitroprusside (SNP), co-administered with 5-HT were examined in the presence or absence of SSAO substrate benzylamine (BZ, 25-500 μM) and the inhibitor semicarbazide (1 mM). Responses were compared before and after treatments using Student's paired t-test.

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Results 

BZ at concentrations below 500 μM did not affect CCh or SNP-induced vasodilatory responses, significantly. 5-HT pressor response, however, was potentiated by 294.4 ± 35.4% (P<0.01) in response to BZ (100 μM). CCh-induced vasodilatory responses were significantly inhibited (60.5 ± 9.5% inhibition; P<0.05) by BZ (500 μM); an effect that was reversed by semicarbazide. SNP-induced responses, however, were not affected by BZ.

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Discussion 

These results indicate that metabolism of BZ by equine digital vessel SSAO leads to impairment of CCh-induced endothelium-dependent vasodilatory responses. Metabolism of BZ also potentiates vasoconstrictor responses to 5-HT, which may have implications in the development of laminitis.

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Conclusion, Clinical Relevance & Take Home Message 

Increased availability of substrates and /or SSAO activity may exacerbate endothelial dysfunction in certain animals.