Impaired cAMP signaling does not account for the attenuated EDHF-mediated dilations in female rat middle cerebral artery

Dilations to endothelium-derived hyperpolarizing factor (EDHF) are significantly attenuated in the middle cerebral artery (MCA) isolated from female compared to male rats. Since gap junctions appear to be involved in the EDHF pathway and cAMP has been shown to enhance gap junction permeability, we tested the hypothesis that elevation of cAMP would enhance EDHF-mediated dilations in female rat MCA. Vascular diameter was measured in perfused MCA segments using videomicroscopy in the presence and absence of IBMX, an inhibitor of cAMP phosphodiesterase. In the presence of l-NAME and indomethacin, dilation to 10− 4 M ATP was significantly reduced in females (48 ± 12%) compared to males (92 ± 2%). IBMX, an inhibitor of cAMP phosphodiesterase, had no significant effect on ATP-mediated dilations in both males and females. Basal cAMP levels were comparable in male and female MCAs (1.7 pmol/mg protein). Incubation with IBMX (2 × 10− 4 M) significantly elevated cAMP in both male (12.8 pmol/mg protein) and female (11.2 pmol/mg protein) MCAs. Our results demonstrate that reduced EDHF dilations in female rat MCA cannot be solely attributed to impaired cAMP signaling. Future studies will target other potential sites along the EDHF pathway in order to identify why EDHF dilations are reduced in the female compared to the male rat MCA.