Using dose‐equivalence theory to quantify endothelial function

Abstract

Currently, evaluation of endothelial function in vitro typically examines a dose‐response to acetylcholine following preconstriction with phenylephrine. However, endothelial modulation of vasoconstrictors, such as angiotensin II, is well known. Our novel methodology derives a dose‐response relationship for this endothelium‐dependent component of action (EDC), which can be fit to a standard four‐parameter dose response equation. Our method is advantageous in that it can provide quantitative information about the EDC of overt vasoconstrictors, and thus does not require the confounding presence of another agonist. In addition, further testing with L‐NAME and IP receptor antagonists can provide information about the agonist‐specific mechanism of the EDC. This may prove useful, since the standard method (acetylcholine vasodilatory response) is primarily nitric oxide (NO)‐dependent in rat aorta, and thus is limited to measuring changes in eNOS function or NO bioavailability. In addition, our methodology allows for statistical evaluation of changes in endothelial function in response to disease and/or treatments, with respect to individual agonists. Four endogenous mediators of vessel tone are examined: angiotensin II, endothelin‐1, norepinephrine, and urotensin II. Research supported by NIDA T32 DA07237