Inverse relationship between arterial tone and vasodilator sensitivity

Abstract

Most small arteries in vivo operate in a state of partial constriction, or tone, which also subjects the endothelium to biaxial deformation. This study tested the hypothesis that the preexisting level of tone is an important determinant of vasodilator sensitivity. Rat uterine resistance arteries (n=12) were cannulated and pressurized to 50 mmHg. Following equilibration, vessels were preconstricted with phenylephrine to reduce initial diameter by 20‐40% (low tone) or 60‐80% (high tone) prior to the addition of SNP (NO donor that acts directly on smooth muscle) or ACh (direct stimulant of endothelial NO release). EC50 values were used as an index of vasodilator sensitivity. Arteries with high levels of tone were significantly less sensitive to both vasodilators than those with low tone, such that the ratio of EC50 values (high vs. low tone) were 17:1 for SNP, but only 6.2:1 for ACh. There was also strong inverse correlation between wall tension and EC50 values, with r2 values of 0.5 and 0.7 for SNP and ACh, respectively. These results highlight the importance of wall tension in modulating arterial vasodilatory responses as a function of tone, and suggest that cellular deformation secondary to vasoconstriction may augment endothelial dilator release, as proportionately less stimulus was required to produce an equivalent amount of vascular smooth muscle relaxation in response to ACh vs. SNP.