Effect of Pentoxifylline and Losartan on insulin resistant equine digital vessels

Abstract

Insulin response on normal blood vessel is a relaxation. However, insulin produces contraction in insulin‐resistant (IR) vessels. IR has been associated with equine laminitis. The objective of this study was to evaluate the effectiveness of two potential drugs (Losartan & Pentoxifylline) to counteract the responses of experimentally induced‐insulin resistant equine digital vessels to insulin in vitro. Palmar digital arteries and veins (2″ long) were collected from lean horses (overnight fasting plasma insulin 65pmol/L and glucose 5.614mmol/L) immediately after euthanasia. Eight 3‐mm wide rings were cut (4 arterial and 4 venous) and were set in in‐vitro tissue baths for response studies. Two rings from each vessel type were made IR by incubating them with insulin at a concentration of 10−5M for 30 min. The other rings were used as control. Then all these rings were contracted with phenylephrine 10−6.5M and when it reached a plateau either losartan (10−5M) or pentoxifylline (10−5M) was added to both insulin resistant and non resistant (control) rings and allowed to stay in the bath for 5 minutes, before a single dose of insulin (10−5M) was added to all rings. The response to insulin was monitored for another 30 minutes. Losartan pre‐treatment of IR vessels produced contraction to insulin. On the contrary, pentoxifylline caused relaxation suggesting it could be beneficial in the treatment of equine laminitis. The study was supported by USDA 1433 Formula ‐ LSU‐SVM.