Role of endothelium-derived hyperpolarizing factor in relaxation of pregnant rat uterine artery by corticotropin-releasing factor

Corticotropin-releasing factor (CRF) a vasorelaxant peptide hormone, is increased during human pregnancy. It is thought to be important in modulating uteroplacental blood flow. CRF causes relaxation by endothelium-dependent as well as -independent mechanisms in the rat aorta. Experiments were designed to evaluate the role of endothelium-derived hyperpolarizing factor, nitric oxide and prostacyclin in the relaxation of the pregnant rat uterine artery by CRF. Segments of the uterine artery (outer diameter 300-400 mum) from day 18 pregnant rats were suspended in a small vessel myograph in physiological salt solution, contracted with norepinephrine or depolarizing solution, and the relaxations to cumulative concentrations of CRF were studied. CRF relaxed the uterine artery in a concentration dependent manner. Mechanical removal of the endothelium decreased the CRF-induced relaxation. Use of depolarizing solution for contraction as well as incubation with thiopental sodium (a cytochrome P-450 inhibitor) prior to contraction with norepinephrine significantly inhibited the relaxation to CRF. Similarly, incubation with N-omega-nitro-L-arginine methyl ester (a nitric oxide synthase inhibitor) decreased CRF responses. In contrast, indomethacin (a cyclooxygenase inhibitor) failed to inhibit the relaxation by CRF. Therefore, these data support a role for endothelium-derived hyperpolarizing factor and nitric oxide but not prostacyclin in relaxation of the pregnant rat uterine artery by CRF.