Up-regulation of pressure-activated Ca(2+)-permeable cation channel in intact vascular endothelium of hypertensive rats.
In endothelial cells, stretch-activated cation channels have been proposed to act as mechanosensors for changes in hemodynamic forces. We have identified a novel mechanosensitive pressure-activated channel in intact endothelium from rat aorta and mesenteric artery. The 18-pS cation channel responded with a multifold increase in channel activity when positive pressure was applied to the luminal cell surface with the patch pipette and inactivated at negative pipette pressure. Channel permeability ratio for K+, Na+, and Ca2+ ions was 1:0.98:0.23. Ca2+ influx through the channel was sufficient to activate a neighboring Ca2(+)-dependent K+ channel. Hemodynamic forces are chronically disturbed in arterial hypertension. Endothelial cell dysfunction has been implicated in the pathogenesis of arterial hypertension. In two comparative studies, density of the pressure-activated channel was found to be significantly higher in spontaneously hypertensive rats and renovascular hypertensive rats compared with their respective normotensive controls. Channel activity presumably leads to mechanosensitive Ca2+ influx and induces cell hyperpolarization by K+ channel activity. Both Ca2+ influx and hyperpolarization are known to induce a vasodilatory endothelial response by stimulating endothelial nitric oxide (NO) production. Up-regulation of channel density in hypertension could, therefore, represent a counterregulatory mechanism of vascular endothelium.
Hoyer
J
J
Division of Nephrology, University Hospital Benjamin Franklin, Free University of Berlin, Germany.
Köhler
R
R
Haase
W
W
Distler
A
A
D000818:Animals; D002118:Calcium / Q000502:physiology; D015220:Calcium Channels / Q000502:physiology*; D004730:Endothelium, Vascular / Q000503:physiopathology*; D006439:Hemodynamics; D006874:Hydrostatic Pressure; D006973:Hypertension / Q000473:pathology / Q000503:physiopathology*; D006977:Hypertension, Renal / Q000473:pathology / Q000503:physiopathology; D066298:In Vitro Techniques; D008465:Mechanoreceptors / Q000502:physiology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D015854:Up-Regulation
D015220:Calcium Channels; D002118:Calcium