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.
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.
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.
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.
Conclusion, Clinical Relevance & Take Home Message
Increased availability of substrates and /or SSAO activity may exacerbate endothelial dysfunction in certain animals.
1Royal Veterinary College, Royal College Street, London, UK
2Faculty of Veterinary Science, University of Melbourne, Victoria 3010, Australia
3Equine Studies Group, WALTHAM Centre for Pet Nutrition, Melton Mowbray, UK
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