Effect of lithium of responsiveness of rat uterine smooth muscle to angiotensin.

Studies were carried out to investigate the effect of Na+ deprivation on the response of rat uterine smooth muscle to angiotensin II (AII). Replacement of Na+ with Li+ in a low-Ca2+-, Mg2+-free solution resulted in a concentration-dependent inhibition of both AII and acetylcholine (ACh)-induced contractions. Inhibition was noted at 10% Li+ substitution and was usually complete when 50% of the Na+ was replaced by Li+. The inhibition was not observed when an equivalent amount of tris(hyroxymethyl)aminomethand (Tris+) or sucrose was used to replace Na+. However, elevation of Ca2+ concentration from 0.2 to 0.5 mM did prevent full expression of the Li+ inhibition of AII. The Li+ effect was rapid in onset (60% inhibition after 5 min preincubation) and readily reversible following removal of the Li+. If, however, the tissue was placed in a depolarizing solution (151 mM KCL), Li+ inhibition of AII WAS NO LONGER OBSERVED. These results are interpreted to mean that Li+ interferes with an essential Ca2+-dependent step involved in membrane excitation following agonist-receptor interaction. The results are discussed in relation to a previously suggested model for AII-induced contractions in this tissue.