Endothelium-dependent circulatory control--a mechanism for the differing peripheral vascular effects of isoflurane versus halothane.
Several studies have suggested that halothane and isoflurane modify responses to endothelium-dependent vasodilators, indicating that the differing circulatory effects of these anesthetics may be, in part, attributable to alterations in endothelial cell control of vascular tone. This study was designed to determine the contribution of endothelium-derived relaxing factor (EDRF/NO) to circulatory control in indomethacin-treated rats anesthetized with equipotent concentrations (1 MAC) of either isoflurane (n = 6) or halothane (n = 8). Using radiolabelled microspheres, systemic and regional hemodynamics were measured in cerebrum, cerebellum, heart, kidney, gastrointestinal tract, spleen, liver, skeletal muscle, skin, ear, and white and brown fat. Cardiac output, mean arterial pressure (MAP), systemic vascular resistance (SVR), regional blood flows, and regional vascular resistances were determined before (control) and after administration of NG-monomethyl-L-arginine (L-NMMA, 100 mg/kg) to inhibit EDRF/NO synthesis, and following L-arginine (300 mg/kg) to reverse the effects of L-NMMA. In both anesthetic groups, L-NMMA decreased cardiac output and increased MAP, SVR, and regional resistances in brain, heart, kidney, spleen, gastrointestinal tract, hepatic artery, skeletal muscle, skin, and white fat. L-arginine returned SVR and MAP to or below control values in both groups, although cardiac output remained decreased. During isoflurane as compared to halothane anesthesia, L-NMMA caused significantly greater increases in blood pressure (54 +/- 7% vs. 24 +/- 2%) and SVR (143 +/- 22% vs. 79 +/- 11%). In addition, rats anesthetized with isoflurane had significantly greater increases in vascular resistance in heart, kidney, gastrointestinal tract, hepatic artery, and skin after L-NMMA than did rats anesthetized with halothane.(ABSTRACT TRUNCATED AT 250 WORDS)
Greenblatt
E P
EP
Department of Anesthesia, University of Pennsylvania School of Medicine, Philadelphia 19104-4283.
Loeb
A L
AL
Longnecker
D E
DE
D000769:Anesthesia, Inhalation; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology; D006221:Halothane; D006439:Hemodynamics / Q000187:drug effects* / Q000502:physiology; D007530:Isoflurane; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology; D019323:omega-N-Methylarginine
D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine; D007530:Isoflurane; D006221:Halothane