Mechanotransduction in hypertensive pulmonary edema

Hypertensive pulmonary edema (HPE) occurs acutely, can be life threatening and is typically associated with normal left ventricular performance. Factors other than simple Starling forces may contribute to the molecular mechanisms by which increased blood pressure leads to acute endothelial barrier failure and lung edema. Herein we investigated the contribution of the endothelial glycocalyx and mechanotransduction pathway(s) to HPE. Methods To mimic an adrenergically‐mediated hypertensive crisis, we administered norepinephrine (NE) to rats and assessed indices of edema development. Rats were anesthetized with isoflurane and mechanically‐ventilated; animals received an infusion of NE to target a MAP = 150mmHg. Lung wet/dry ratio, DPaO 2 , plasma hematocrit, plasma volume, lung and BAL MPO activity and lung histological injury were assessed. Albumin transport was assessed in vitro . Inhibition of nitric oxide synthase (NOS) by L‐NAME was used to test the contribution of endothelial mechanotransduction to edema development. Wet/dry ratio was determined in Glypican‐1 −/− and Syndecan‐1 −/− isolated perfused lungs exposed to low and high pressure to evidence the role of the glycocalyx in pressure‐induced edema. Results NE‐treated rats had a decrease in PaO 2 and in plasma volume, an increase in lung wet/dry ratio, plasma hematocrit levels and in lung injury histological score; MPO activity was not altered. L‐NAME significantly attenuated NE‐induced pulmonary edema. Glypican‐1 −/− and Syndecan‐1 −/− mice were protected from pressure‐induced pulmonary edema. In vitro , albumin uptake and transport was increased by pressure but not by NE; effect inhibited by L‐NAME. Conclusion These results reveal a determinant role of the glycocalyx in the molecular mechanisms that signal to HPE development.