Figure 4.

Dilation of the ex vivo ductus arteriosus by loop diuretics. The surgically isolated ductus arteriosus of term gestation fetal mice was mounted on 150 μm cannulae and studied by pressure myography {Reese, 2009 1224 /id}. Exposure to increasing doses of furosemide produced concentration-dependent relaxation of the ductus arteriosus (not shown), whereas exposure to bumetanide had little effect on ductus tone. At the highest concentration (10⁻³ M), furosemide, which inhibits the GABA-A chloride channel and both of the NKCC isoforms, induced approximately 25% increase in ductus diameter compared to resting baseline tone (p<0.01) and significantly greater than bumetanide (p<0.01). Bumetanide, an NKCC1-specific inhibitor, had no significant effect on ductus diameter compared to baseline.