The relaxation responses to corticotropin-releasing factor in rat aorta are endothelium dependent and gestationally regulated

OBJECTIVE: Our purpose was to examine the hypothesis that the relaxant response to corticotropin releasing factor is endothelium dependent and changes during pregnancy. STUDY DESIGN: Relaxant responses to cumulative concentrations of corticotropin-releasing hormone were measured in rings of thoracic aorta, precontracted with phenylephrine, from pregnant and nonpregnant female rats. Each group consisted of 5 to 10 rats. RESULTS: The relaxation induced by corticotropin-releasing factor in aortic rings from nonpregnant rats decreased after deendothelization and treatment with N-omega-nitro-L-arginine methyl ester (a nitric oxide synthase inhibitor), LY-83,583 (a guanylate cyclase inhibitor), or alpha-helical corticotropin-releasing factor 9-41 (a corticotropin-releasing factor antagonist). The percent decrease in relaxation at 1 nmol/L of corticotropin-releasing factor was about 88% with deendothelization, 100% with N-omega-nitro-L-arginine methyl ester, 76% with LY-83,583, and 100% with a-helical corticotropin-releasing factor 9-41. The ;responses to corticotropin-releasing factor in intact rings from rats in early pregnancy were not significantly different from those in the nonpregnant female rats, but the responses were decreased during the later stages of gestation (percent decrease in relaxation at 1 nmol/L of corticotropin-releasing factor about 71% at day 20 and 98% at term). The relaxation induced by corticotropin-releasing factor during pregnancy was also inhibited by deendothelization, N-omega-nitro-L-arginine methyl ester, or LY-83,583. CONCLUSIONS: The relaxant response to corticotropin-releasing factor in the rat aorta is endothelium dependent and is mediated by the nitric oxide-cyclic guanosine monophosphate pathway. The receptor involved in this effect is alpha-helical corticotropin-releasing factor 9-41 sensitive. This inhibitory response is unchanged during early pregnancy but reduced toward the end of gestation.