Increased mechanosensitive currents in aortic endothelial cells from genetically hypertensive rats.

OBJECTIVE

To characterize and compare mechanosensitive cell currents in rat aortic endothelial cells from spontaneously hypertensive and Wistar-Kyoto rats.

METHODS AND

RESULTS

By use of the patch-clamp technique, we investigated whole-cell currents of native rat aortic endothelial cells in the presence of mechanical stimulation elicited by hyposmotic cell swelling. In rat aortic endothelial cells, this hypotonic cell swelling induced a fourfold increase in outward-directed whole-cell currents carried by K+, leading to cell hyperpolarization and a small increase in inward-directed currents. Gadolinium, a blocker of stretch-activated cation channels, completely blocked hypotonic cell swelling-induced outward- and inward-directed whole-cell currents. Charybdotoxin, a blocker of Ca(2+)-dependent K+ channels, decreased hypotonic cell swelling-induced outward-directed currents by up to 85%. Disruption of actin filaments by cytochalasin B and of microtubuli by nocodazole reduced the activation of hypotonic cell swelling-induced whole-cell currents by 91 and 71%, respectively. In experimental hypertension, hypotonic cell swelling-induced whole-cell conductance was significantly increased in spontaneously hypertensive rats (331 +/- 20 pS/pF) compared with normotensive controls (167 +/- 7 pS/pF, P < 0.01), whereas basal and agonist-induced cell conductances were not altered.

CONCLUSIONS

Increased hypotonic swelling-induced currents in aortic endothelial cells from spontaneously hypertensive rats presumably reflect an increased density or mechanosensitivity of stretch-activated ion channels in experimental hypertension. The increased mechanosensitive whole-cell currents might indicate an altered endothelial mechanotransduction in experimental hypertension.