IMPAIRED CYCLIC NUCLEOTIDE-DEPENDENT VASORELAXATION IN HUMAN UMBILICAL ARTERY SMOOTH-MUSCLE

Activation of either the adenylate cyclase pathway with forskolin or t he guanylate cyclase pathway with sodium nitroprusside fails to induce active relaxation of serotonin-precontracted human umbilical artery s mooth muscle (HUASM) but causes active relaxation of serotonin-precont racted bovine carotid artery smooth muscle (BCASM). This difference in response appears to be unique to HUASM in that all other vascular mus cles exhibit relaxation in response to these substances. Forskolin and sodium nitroprusside stimulation leads to respective increases in int racellular adenosine 3',5'-cyclic monophosphate (cAMP) and guanosine 3 ',5'-cyclic monophosphate (cGMP) concentrations in HUASM and BCASM, cA MP- and cGMP-dependent protein kinases are both present in HUASM and c an be activated in homogenates of HUASM by the addition of exogenous c AMP and cGMP, respectively. When either forskolin or nitroprusside act s in BCASM, two low-molecular-weight proteins display an increase in t he extent of phosphorylation. Neither protein shows such an increase w hen HUASM is treated with either agent. Thus the inability of HUASM to display active relaxation appears to be secondary to impaired activat ion of cyclic nucleotide-dependent protein kinases. The refractoriness to active relaxation may contribute to the vasospasm that occurs in t he umbilical vasculature with parturition.