In vitro pharmacologic effect of two endothelin-1 antagonists on equine colonic arteries and veins.

This study sought to assess how effective two potential endothelin-1 (ET-1) antagonists are at blocking the contractile responses of horse colonic vessels to varying concentrations of ET-1. The study found that both antagonists successfully blocked the ET-1-induced contractions, with one antagonist demonstrating superior effectiveness due to its water solubility and complete blockade at a specific concentration.

Methods Used in the Research

• The study utilized mesenteric vessels from six clinically healthy horses.
• A set-up was prepared in organ baths containing an oxygenated Tyrode solution at 37 degrees Celsius, with arterial and venous rings from the colonic vessels suspended in the solution.
• The vessel rings were subjected to a tension of 2 grams and allowed to equilibrate for 45 minutes before any conclusions were drawn.
• The antagonists B-1 (PD 142893) and B-2 (PD 145065), which are potential ET-1 inhibitors, were then tested on the vessels.
• Concentration-response relationships of ET-1 were established using a control ring from each type of vessel.
• Three vessel rings of each type were exposed to three different concentrations of each antagonist before the ET-induced contractions were measured.
• The maximum contractile response and pA2 values (which indicate potency) were determined for each trial.

Results of the Research

• The study found that the vessel contractions in response to ET-1 were dependent on the concentration. Specifically, arteries responded slowly but ended with stronger contractions, while the veins responded immediately with sustained contractions.
• Both antagonists effectively inhibited the contractions in a concentration-dependent manner, with significant differences observed at 10(-6) and 10(-5)M for arteries and 10(-5)M for veins.
• The antagonist B-2 completely blocked the contractions at a concentration of 10(-5)M.
• pA2 values for B-1 were 8.26 and 6.82 for arteries and veins respectively, and 8.25 and 7.21 for B-2.

Conclusions from the Research

• Based on the findings, both antagonists effectively blocked the ET-1-induced contractions in the equine colonic vessels.
• However, the B-2 antagonist, being water-soluble and able to completely block contractions at a concentration of 10(-5) M, appears to be the preferred choice of antagonist.