Evidence of Reduced Myoendothelial Coupling in Female Rat Middle Cerebral Artery during EDHF Stimulation

In the rat middle cerebral artery (MCA), dilations to endothelium‐derived hyperpolarizing factor (EDHF) are less in females compared to males. Since myoendothelial gap junctions (MEGJs) appear to play an important role in the EDHF response in males, we hypothesized that reduced myoendothelial coupling accounts for the attenuated EDHF response in female rat MCA. Membrane potential in endothelium was measured using the voltage‐sensitive dye di‐8‐ANEPPS and in smooth muscle using intracellular glass microelectrodes in the presence of L‐NAME and indomethacin. Electron microscopy was used to assess MEGJs. In endothelial cells, the di‐8‐ANEPPS fluorescence ratio change to 10 −5 M UTP was similar in males (−2.9±0.5%) and females (−3.2±0.2%), indicating comparable degrees of endothelial cell hyperpolarization. However, smooth muscle cell hyperpolarization to 10 −5 M UTP was significantly attenuated in females (−31±1.5mV pre‐UTP and −31 ±1.6mV post‐UTP) compared to males (−28±1.7mV pre‐UTP and −36±1.8mV post‐UTP). Frequency of MEGJs was comparable in males (2.0±0.5 MEGJ/5um vessel length) and females (2.1±1.4 MEGJ/5um vessel length). Our results suggest that in rat MCA, communication between endothelium and smooth muscle is impaired in females compared to males. While the number of MEGJs does not appear to be implicated, it is possible that MEGJ conductance is reduced in females. Supported by NIH HL72954.