ROLE OF PROSTAGLANDIN E(2) IN ALTERATIONS OF THE BETA-ADRENERGIC SYSTEM FROM RAT ECLAMPTIC UTERUS

The inotropic effect of isoproterenol, as well as the B-adrenoceptor population, was measured in pregnant uterine tissue from female spontaneous hypertensive rats (SHR) (control group: C) and female SHR that were grafted with skin from Holtzman male rats (eclamptic group: E). The K-d value of the concentration-response curve of isoproterenol was higher for uteri from E rats than C rats. This phenomenon was not accompanied by a modification in the expression of beta-adrenoceptors. Inhibition of the synthesis of prostaglandins prevented the hyporeactivity to isoproterenol during eclampsia. Moreover, uteri from E rats generated and released greater amounts of prostaglandin E(2) (PGE(2)) than uteri from C rats, even in the presence or absence of isoproterenol. In addition, whereas isoproterenol administered alone increased basal cyclic AMP (cAMP) production from C uteri, PGE(2) administered alone enhanced cAMP production in E uterine tissue. These results suggest that the decrease in beta-adrenergic response to the agonist in E rats is ascribed to PGE(2) production. The abnormal reactivity to the beta-agonist could be associated with a heterologous desensitization of uterine beta-adrenoceptors exerted by PGE(2) overload in uteri from E rats. These results bear directly on the regulation of uterine motility during pregnancy, since an impaired response to beta-adrenergic innervation could lead to increased uterine motility, impairing the maintenance of pregnancy.