Abstract
Epithelial Na+ Channel (ENaC) and Acid Sensing Ion Channel (ASIC) proteins are thought to be required for mechano‐dependent responses, such as migration of vascular smooth muscle cells. We tested the hypothesis that ENaC/ASIC proteins are required for angiogenesis, a response dependent on vascular/endothelial cell migration. Aortic rings from 78 g Fisher rats were embedded in rat tail collagen and incubated at 37° C in 20% O2/5% CO2 for 8 days. Cultures were fed daily with serum‐free media (EBM, Lonza) containing benzamil (10 μM); control cultures received media containing an equal volume of vehicle. In control cultures (n=23), the number of microvessels (MVs) reached a peak value of 81±6 (mean±SE) on day 5, and then decreased progressively for the next 3 days as shown. Cultures treated with benzamil (n=18) showed an early peak in MV growth on day 4 (58±7) followed by MV regression on days 5‐8. Inhibition of ENaC/ASIC activity with 10 μM benzamil decreased MV number by 32±9% on day 5 (p<0.05), 32±6% on day 6 (p<0.05), and 45±4% on day 7 (p<0.01). The results are consistent with the hypothesis that ENaC/ASIC proteins are required for normal MV growth or maintenance of MVs in the rat aortic ring assay. (Supported by HL‐51971)
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