Response of descending vasa recta to luminal pressure

We tested whether luminal perfusion and pressurization induce an endothelial cytoplasmic Ca(2+) ([Ca(2+)](CYT)) response in descending vasa recta (DVR). DVR isolated from the rat outer medulla were cannulated and subjected to free-flow microperfusion (5 nl/min); the onset of which increased [Ca(2+)](CYT) from a baseline of 76 +/- 13 to 221 +/- 65 nM. A graded increase in luminal pressure from 0 to 45 mmHg in stopped-flow experiments induced a parallel increase in [Ca(2+)](CYT) from a baseline of 74 +/- 24 to 194 +/- 33 nM at 45 mmHg, with a tendency for [Ca(2+)](CYT) to plateau at pressures >25 mmHg. The removal of extracellular Ca(2+) and blockade by either La(3+) (10 microM) or SKF-96365 (100 microM) eliminated the response. Luminal pressurization to 25 mmHg increased nitric oxide (NO) generation, a response blocked by NO synthase inhibition or removal of extracellular Ca(2+). The NO generation was not affected by the superoxide dismutase mimetic tempol. We conclude that DVR endothelia are mechanosensitive and respond to luminal pressure by elevating [Ca(2+)](CYT) and generating NO. That response might augment medullary perfusion and saliuresis.