Background and Objectives. Human umbilical vessels are sensitive to local anesthetic agents as well as to a variety of other exogenous and endogenous substances. Changes in blood gases such as hypoxia and hypercarbia may alter these responses. This study examined the effects of local anesthetic agents under these conditions and how the effects are related to the vascular endothelium.

Methods. Veins and arteries, dissected from umbilical cords of healthy newborns, were cross-sectioned to form rings. The rings were mounted in a muscle chamber containing Krebs-Ringer bicarbonate solution that was gassed to approximate control, low Po₂ or hypercarbic conditions. Changes in isometric tension were recorded in response to increasing concentrations of bupivacaine (B), lidocaine (L), or 2-chloroprocaine (2-CP). In half the experiments, intimal rubbing was used to remove the endothelium of rings for the purpose of disclosing the role of endothelial-derived factors.

Results. The normal contracting (increasing baseline tone) or relaxing (decreasing baseline tone) responses to local anesthesia were unchanged by hypercarbia, but low Po₂ suppressed the relaxing effect of 2-CP on arteries. Removal of endothelium enhanced the relaxing effect of 2-CP on arteries, and unmasked a contracting effect of L on arteries. Rubbed vessels, while exposed to low Po₂ or hypercarbia, became less responsive to 2-CP.

Conclusions. Changes in the internal environment are capable of altering the response of umbilical vascular smooth muscle to local anesthesia. Additionally, the vascular endothelium appears to influence the degree of response to anesthesia.