COMPARATIVE EFFECTS OF NITRIC-OXIDE INHIBITION ON THE CORONARY VASOMOTOR RESPONSES TO ETOMIDATE, PROPOFOL, AND THIOPENTAL IN ANESTHETIZED DOGS

We examined the hypothesis that the coronary vasomotor responses to et omidate (ETO), propofol (PRO), and sodium thiopental (STP) are mediate d through contrasting effects on the resting nitric oxide (NO)dependen t vasodilator tone that opposes adrenergic vasoconstrictor activity in the intact dog. Circumflex flow (CxF) responses to randomized intraco ronary microinjections (0.3 mL) of normal saline (NS), alkalinized sal ine (AS), intralipid (IL), adenosine (ADE, 17 mu g), acetylcholine (AC h, 1.25 mu g), ETO (6, 12, 60 mu g), PRO (30, 60, 300 mu g), and STP ( 75, 150, 750 mu g) were quantified in eight isoflurane-anesthetized do gs with fixed ventricular rates (100 bpm). Injections were repeated du ring intravenous (TV) infusion (50 mg/kg + 1 mg.kg(-1).min(-1)) of NG- nitro-L-arginine methyl ester (LNAME), ADE and ACh transiently increas ed CxF to 305% +/- 20% (P < 0.001) and 310% +/- 29% (P < 0.001) of res ting values, respectively. ETO had no effect, whereas PRO (300 mu g) p rovoked small transient increases in CxF to 135% +/- 4% (P < 0.05) of control. Responses to STP (750 mu g) were characterized by momentary d ecreases to 74% +/- 4% (P < 0.001), followed immediately by increases to 183% +/- 11% (P < 0.001) of resting values; NS AS, and IL had no ef fect. The momentary decreases with STP (750 mu g) were significantly a ugmented during NO inhibition with CxF declining to 49% +/- 7% (P < 0. 001) of resting values, whereas the secondary increase was unchanged. With L-NAME, CxF responses to ACh were attenuated to 32% +/- 3% (P < 0 .001) of control, whereas responses to ADE, ETO, and PRO were unchange d. PRO caused small but significant increases in CxF that appear to be NO-independent, whereas NO inhibition accentuated the initial vasocon strictor response to STP but had no effect on the secondary phase vaso dilation. The data suggest that STP may evoke reductions in coronary f low that are profoundly exaggerated under conditions of coronary endot helial dysfunction.