Abstract

We have evaluated the hypothesis that vasoactive hormones increase cellular cyclic AMP (cAMP) levels in cultured vascular smooth muscle cells from rat mesenteric arteries by stimulating endogenous prostaglandin (PG) synthesis. Vasopressin and angiotensin II, which were shown previously to provoke the synthesis of PGs in cultured vascular smooth muscle cells, increased cellular cAMP concentrations by about 2-fold, whereas a peptide analog of vasopressin, 1-desamino-8-D-arginine vasopressin, mostly lacking vasopressin's ability to elicit PG synthesis, was ineffective. Two other chemically dissimilar effectors that provoked the synthesis of PGs in cultured vascular smooth muscle cells, namely arachidonate and ionophore A23187, also increased cellular cAMP levels. The increase of cAMP by vasopressin and angiotensin II was transient, reaching a maximum at 1 to 2 min of incubation, followed by a decline to basal levels. Acetylsalicylic acid, a specific inhibitor of PG synthesis, completely prevented vasopressin- and arachidonate-evoked increases of cAMP but did not affect basal cAMP concentrations. Exogenous prostacyclin and prostaglandin E2 dose-dependently increased cAMP concentrations although prostacyclin was more effective than prostaglandin E2. The ability of exogenous prostacyclin to evoke cAMP increases was not inhibited by acetylsalicylic acid. The results support the hypothesis that the stimulation of endogenous PG synthesis by vasoactive hormones in turn modulates cellular cAMP levels in cultured vascular smooth muscle cells from rat mesenteric arteries.