Endothelin activation of reactive oxygen species mediates stress-induced pressor response in Dahl salt-sensitive prehypertensive rats.
Experiments were designed to test the hypothesis that endothelin (ET) and/or reactive oxygen species contribute to the pressor response induced by acute air jet stress in normotensive Dahl salt-sensitive rats maintained on a normal salt diet (prehypertensive). Mean arterial pressure was chronically monitored by telemetry before and after 3-day treatment with the free radical scavenger 4-hydroxy-2,2,6,6-tetramethyl piperidinoxyl (Tempol) or ET receptor antagonists ABT-627 (ET A antagonist) or A-182086 (ET A/B antagonist) supplied in the drinking water. Rats were restrained and subjected to pulsatile air jet stress (3 minutes). Plasma samples at baseline and during acute stress were analyzed for 8-isoprostane (measure of reactive oxygen species production) and ET. Neither Tempol nor ET receptor antagonist treatment had an effect on baseline mean arterial pressure or plasma 8-isoprostane. The pressor response to acute stress was accompanied by significant increases in plasma 8-isoprostane and ET. Tempol significantly reduced both the total pressor response (area under the curve) and the stress-mediated increase in plasma 8-isoprostane; conversely, Tempol had no effect on the stress-induced increase in plasma ET. Combined ET(A/B) antagonism, but not selective ET(A) receptor blockade, similarly suppressed the pressor response to stress and stress-mediated rise in 8-isoprostane. Together these results indicate that reactive oxygen species contribute to the pressor response to acute air jet stress. Furthermore, the increase in reactive oxygen species occurs downstream of ET(B) receptor activation.
D'Angelo
Gerard
G
Vascular Biology Center, Medical College of Georgia, Augusta, GA 30912, USA.
Loria
Analia S
AS
Pollock
David M
DM
Pollock
Jennifer S
JS
D000818:Animals; D000077868:Atrasentan; D001794:Blood Pressure / Q000187:drug effects; D002250:Carbon Radioisotopes / Q000494:pharmacology; D003497:Cyclic N-Oxides / Q000494:pharmacology; D016232:Endothelins / Q000502:physiology*; D016166:Free Radical Scavengers / Q000494:pharmacology; D006973:Hypertension / Q000503:physiopathology*; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D020303:Rats, Inbred Dahl; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013113:Spin Labels; D013315:Stress, Psychological / Q000503:physiopathology; D013449:Sulfonamides / Q000494:pharmacology
C467893:A 182086; D002250:Carbon Radioisotopes; D003497:Cyclic N-Oxides; D016232:Endothelins; D016166:Free Radical Scavengers; D011759:Pyrrolidines; D017382:Reactive Oxygen Species; D013113:Spin Labels; D013449:Sulfonamides; C001803:tempol; D000077868:Atrasentan