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.


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.
Köhler
R
R
Department of Endocrinology and Nephrology, University Hospital Benjamin Franklin, Free University, Berlin, Germany.
Distler
A
A
Hoyer
J
J
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D002118:Calcium / Q000378:metabolism; D018999:Charybdotoxin / Q000494:pharmacology; D002614:Chelating Agents / Q000494:pharmacology; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D005500:Follow-Up Studies; D006973:Hypertension / Q000235:genetics / Q000378:metabolism*; D008465:Mechanoreceptors / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000378:metabolism*; D011897:Random Allocation; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
D002614:Chelating Agents; D015221:Potassium Channels; D018999:Charybdotoxin; D004533:Egtazic Acid; D000255:Adenosine Triphosphate; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D002118:Calcium