Halothane impairs the hemodynamic influence of endothelium-derived nitric oxide.
BACKGROUND
The endogenous vasodilator endothelium-derived nitric oxide (EDNO) contributes to the regulation of vascular tone and organ perfusion. It has been suggested that some volatile anesthetics may diminish the influence of EDNO and thereby decrease regional blood flow.


METHODS
Radioactive microspheres were used to determine regional hemodynamics in rats. The authors tested the hypothesis that halothane inhibits EDNO and, therefore, should diminish the response to nitric oxide synthesis inhibition by NW-nitro-L-arginine methyl ester (L-NAME) compared with either conscious or barbiturate-anesthetized rats.


RESULTS
NW-nitro-L-arginine methyl ester decreased blood flow to the brain by 23% (P < 0.005) in conscious rats to a level similar to that seen with either anesthetic agent. In both conscious and barbiturate-anesthetized rats, L-NAME increased blood pressure (BP) by 24 +/- 2 (P < 0.001) and 20 +/- 1 (P < 0.001) mmHg and total peripheral resistance (TPR) by 132% (P < 0.001) and 105% (P < 0.001), respectively. In contrast, during halothane anesthesia, both the pressor response (only 7 +/- 1 mmHg) and the increase in TPR (only 22%) were greatly diminished (P < 0.001). NW-nitro-L-arginine methyl ester decreased cardiac output (CO) by 47% (P < 0.001) and heart rate (HR) by 28% (P < 0.001) in conscious rats. In barbiturate-anesthetized rats, L-NAME decreased CO by 38% (P < 0.005) and HR by 13% (P < 0.001). In halothane-anesthetized rats, L-NAME changed neither CO nor HR. Thus halothane anesthesia largely eliminated the systemic response to EDNO synthesis inhibition. In conscious rats, L-NAME decreased blood flow to the heart (30%) and kidneys (47%). In barbiturate-anesthetized rats, L-NAME did not alter blood flow to the heart but decreased renal blood flow by 35% (P < 0.005). In halothane-anesthetized rats, L-NAME did not alter blood flow to either the heart or the kidneys. Overall, halothane blunted or blocked the systemic and regional hemodynamic responses to EDNO synthesis inhibition seen in conscious and barbiturate-anesthetized rats.


CONCLUSIONS
Halothane anesthesia greatly diminished or eliminated all systemic and regional hemodynamic responses to L-NAME. These data indicate that halothane anesthesia inhibits EDNO-mediated regulation of systemic and organ hemodynamics.
Sigmon
D H
DH
Department of Medicine, Henry Ford Hospital, Detroit, Michigan 48202-2689.
Florentino-Pineda
I
I
Van Dyke
R A
RA
Beierwaltes
W H
WH
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors; D002560:Cerebrovascular Circulation / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D006221:Halothane / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects*; D008297:Male; D008863:Microspheres; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D011659:Pulmonary Gas Exchange / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation / Q000187:drug effects; D013874:Thiopental / Q000031:analogs & derivatives / Q000494:pharmacology
C004316:thiobutabarbital; D009569:Nitric Oxide; D001120:Arginine; D013874:Thiopental; D006221:Halothane; D019331:NG-Nitroarginine Methyl Ester