Increased mechanosensitive currents in aortic endothelial cells from genetically hypertensive rats

Abstract

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

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 Ca2+-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.

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.