ABSTRACT
Different endothelium-derived factors are involved i n the regulat ion o f the vasomotor tone, but Endothe l ium-der ived Hyperpo la r i z ing Fac to r ( E D H F ) is par t iculary impl ic ated in the relaxat ion o f the smooth muscle o f distal arteries o f small diameter (Shim o k a w a et al, 1996; G r i f f i t h et al, 1998). The phenomenon k n o w n as E D H F appears to consist o f agonist-mediated hyperpolar iza t ion o f the endothelial cell , fo l lowed by hyperpolar iza t ion o f the under lying smooth muscle cell (Edwards et al, 1999; Y a m a m o t o et al, 1999). Th i s process probably requires close contact between the endothelial and smooth muscle cell layer, thus account ing for the prominence o f E D H F in the thinner-walled mic ro vasculature. F o r this reason, attention has focused on the possible role o f myoendothel ia l gap junct ions as the means whereby the E D H F 's ignal ' is transmitted f rom one cell to another. B lockade o f hyperpolar iza t ion o f smooth muscle cells by using gap junc t ion inhibi tors (Taylor et al, 1998; Y a m a m o t o et al, 1999) highlights the potential importance o f gap junct ions for t ransmission o f E D H F between endothelial and smooth muscle cells. T w o hypotheses have been proposed about the nature o f E D H F . Ei ther E D H F is electrotonically transferred hyperpolar iza t ion v i a gap junct ions f rom endothelial to smooth muscle cells ( Y a m a m o t o et al, 1999), or a chemical factor represents E D H F and the gap junct ions provide a pathway for the movement o f this chemical factor f rom endothelial to smooth muscle cells (Campe l l et al, 1996; R a n d a l l and K e n d a l l , 1998). Indeed, gap junct ions provide a pathway for direct movement o f low-molecular-weight substances between adjacent cells and thereby activate signal t ransduct ion (Gabriels and Pau l , 1998). Endo the l i a l cell-to-endothelial cell and smooth muscle cel l-to-smooth muscle cell junct ions are wel l documented i n systemic b l o o d vessels and i n the m a i n stem o f the pu lmonary artery i n a variety o f species (van K e m p e n and Jongsma, 1999; N a k a m u r a et al, 1999). A l t h o u g h there is functional evidence for myoendothel ia l junct ions in large systemic b l o o d vessels (Li t t le et al, 1995; Bény and Cona t , 1992),
88 M. Koslowski et al
ultrastructural evidence o f myoendothel ia l junct ions in the microvasculature is rare (Svendsen et al, 1990; Sandow and H i l l , 2000). Myoendo the l i a l junct ions have not yet been described in pu lmonary microvessels, the site o f the pu lmonary vascular resistance.
