Etomidate alters calcium mobilization induced by angiotensin II in rat aortic smooth muscle cells.
Etomidate is widely used for induction of anesthesia in the hemodynamically compromised patient, because of its moderate direct effect on arterial vasomotoricity and cardiac function, but its effect on blood pressure regulatory systems is not known. We studied the effect of etomidate (10(-8) to 10(-4) mol.L) on Ca++ mobilization elicited by angiotensin II (Ang II) in cultured aortic smooth muscle cells (VSMC) from 6-week-old Wistar Kyoto rats. Intracellular Ca++ (Cai++) variation was assessed in Fura 2-loaded VSMC, using fluorescent imaging microscopy. Ang II (10(-6) mol.L(-1))-induced transient Cai++ mobilization from internal stores was assessed in the absence of external Ca++. Ca++ influx was assessed upon reintroduction of external Ca++ (10(-3) mol.L(-1)). Etomidate moderately decreased both the amplitude (etomidate 10(-4) mol.L(-1): 68% of control value, P < 0.001) and the slope of Cai++ increase (56% of control, P < 0.001) from internal stores induced by Ang II. PD2 values (PD2 = -log(EC50)) for amplitude and slope were 6.4 +/- 0.7 and 6.0 +/- 0.3, respectively. Ang II-elicited Ca++ influx was also significantly decreased (45% of control, P < 0.001; PD2 = 5.5 +/- 0.3). Etomidate alters the Ca++ mobilization elicited by Ang II in rat aortic VSMC, suggesting that the vascular response to Ang II may be altered during etomidate anesthesia. However, this effect was observed at high concentration of etomidate, and may be limited when low doses of etomidate are used.
Pili-Floury
Sébastien
S
Department of Medical Research, Marie Lannelongue Hospital, University of Paris XI, France.
Samain
Emmanuel
E
Bouillier
Hélène
H
Rucker-Martin
Catherine
C
Safar
Michel
M
Dagher
Georges
G
Marty
Jean
J
Renaud
Jean François
JF
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions / Q000502:physiology; D005045:Etomidate / Q000494:pharmacology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D011921:Rats, Inbred WKY
D000804:Angiotensin II; D005045:Etomidate