P109	The effect of the endothelium on the pressor response to 5-hydroxytryptamine in the isolated Krebs-perfused equine digit.
Y.Berhane, S.Bailey, J.Elliott
Royal Veterinary College, London, GB.

Equine laminitis is thought to be the result of ischaemia and reperfusion injury of the digital dermal lamellae. The vasoactive mediator(s) triggering this disease remain unknown, although it is thought that 5-hydroxytryptamine (5-HT) may play a role. Endothelium-dependent relaxation and/or active uptake of 5-HT may modulate its vasoconstrictor actions. The aim of the present study was to assess the effect of the endothelium on the pressor response to 5-HT in the perfused digit. Hind limbs were obtained from mixed breed healthy adult horses killed at an abattoir. The digital circulation was perfused with Krebs-Henseleit solution and the baseline perfusion pressure was established. Following assessment of the integrity of the endothelium to a bolus dose of carbachol, the increase in the perfusion pressure was recorded in response to an infusion of 5-HT (30 nM) for a period of 10 min, before and after pre-treatment with the nitric oxide synthase inhibitor L-NAME (100 μM), the cyclooxygenase inhibitor ibuprofen (10 μM), the selective 5-HT uptake inhibitor fluvoxamine (1 μM) or the detergent CHAPS (0.3%). Infusion of 5-HT (30 nM) caused a peak increase of 102 ± 8.3 mmHg over baseline (110 ± 8.3 mmHg; n=17). Table 1 shows the effect of the pretreatments (n = 4-6). *P<0.05 vs control compared by paired t-test. Treatment % increase in perfusion pressure(area under the curve) L-NAME 88.7 ± 18.9* Ibuprofen 5.9 ± 3.9 L-NAME + Ibuprofen 83.2 ± 4.2* fluvoxamine 85.5 ± 17.6* CHAPS 132.1 ± 29* The results demonstrate that NO is important modulator of 5-HT pressor response, but not prostacyclin. Inhibition of 5-HT uptake significantly increased the pressor response. Chemical disruption of the endothelium with CHAPS caused greater enhancement of 5-HT pressor response compared to pretreatment with L-NAME or fluvoxamine alone. These data suggest that the endothelium of the equine digital vascular bed modulates the pressor response to 5-HT by a number of mechanisms.

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