Mechanosensitive cation channels in aortic endothelium of normotensive and hypertensive rats.
In response to humoral and hemodynamic stimuli, vascular endothelium regulates vascular tone by releasing endothelium-derived vasoactive factors. Stretch-activated cation channels have been postulated to act as endothelial mechanosensors that respond to changes in hemodynamic forces. We report the presence of a nonselective (n=98) and K+-selective (n=53) stretch-activated channel in rat intact aortic endothelium and isolated aortic endothelial cells. The nonselective channel showed a permeability ratio for Na+, K+, and Ca2+ of 1:0.95:0.23 and was completely blocked by 50 micromol/L gadolinium, a blocker of stretch-activated channels. The K+-selective channel was selectively permeable for K+, with a K+-Na+ permeability ratio of 10.9:1. In whole-cell current recordings, hyposmotic cell swelling induced an increase in cell conductance. The swelling-induced current was completely blocked by 50 micromol/L gadolinium, showing that stretch-activated channels were activated by cell swelling and carry macroscopic cell currents. In a comparative study with normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR), the K+-selective stretch-activated channel was observed in a 4.4-fold higher density in adult SHR compared with WKY. Also, in adult SHR, the stretch sensitivity of the nonselective channel was nearly twice as high as in WKY. In contrast, channel properties were unchanged in young SHR (5 to 6 weeks old) compared with age-matched WKY. These data suggest that stretch-activated channels are regulated in their sensitivity and density when subjected to increased hemodynamic forces such as in hypertension. Since the channels are capable of acting as endothelial mechanosensors, the altered channel properties might contribute to an altered mechanoreception in hypertension.
Hoyer
J
J
Department of Internal Medicine and Nephrology, University Hospital Benjamin Franklin, Free University, Berlin, Germany.
Köhler
R
R
Distler
A
A
D000367:Age Factors; D000818:Animals; D001013:Aorta, Thoracic; D002118:Calcium / Q000378:metabolism; D002412:Cations; D004730:Endothelium, Vascular / Q000166:cytology / Q000503:physiopathology*; D006439:Hemodynamics; D006973:Hypertension / Q000503:physiopathology*; D066298:In Vitro Techniques; D007473:Ion Channels / Q000378:metabolism / Q000502:physiology*; D008465:Mechanoreceptors / Q000502:physiology*; D018408:Patch-Clamp Techniques; D010539:Permeability; D011188:Potassium / Q000378:metabolism; D015221:Potassium Channels / Q000378:metabolism / Q000502:physiology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012964:Sodium / Q000378:metabolism
D002412:Cations; D007473:Ion Channels; D015221:Potassium Channels; D012964:Sodium; D011188:Potassium; D002118:Calcium