Volatile anesthetics do not alter bradykinin-induced release of nitric oxide or L-citrulline in crystalloid perfused guinea pig hearts. Anesthesiology 1998 Aug;89(2):421-33
Date
08/26/1998Pubmed ID
9710401DOI
10.1097/00000542-199808000-00019Scopus ID
2-s2.0-0031830498 (requires institutional sign-in at Scopus site) 14 CitationsAbstract
BACKGROUND: Nitric oxide (NO) and L-citrulline (L-cit) are released by endothelial NO synthase (eNOS) to induce vasodilation via guanylyl cyclase and cyclic guanosine monophosphate (cGMP). Volatile anesthetics directly reduce vascular muscle tone, but their effects on the eNOS cGMP pathway is controversial. The aim of this study was to examine the effects of anesthetics on bradykinin-induced increases in flow, NO, and L-cit in isolated hearts.
METHODS: Guinea pig hearts were isolated, perfused at 55 mmHg with a crystalloid or erythrocyte perfusate at 37 degrees C, and heart rate, left ventricular pressure, coronary flow (CF), effluent pH, and oxygen tension were monitored. Effluent [NO] was measured by a Clark-type electrode (sensitivity > or = 1 nM = 3 pA) with a selectively permeable membrane. Effluent [L-cit] was measured by chromatography. Before, during, and after exposure to halothane, isoflurane, or sevoflurane, hearts were infused with as much as 100 nM bradykinin to induce increases in CF and effluent release of NO and L-cit.
RESULTS: In crystalloid-perfused hearts, 10 nm bradykinin produced maximal concentration-dependent increases in CF (87+/-2%), [NO] (24+/-4 nM), NO release (128+/-18 pmol x g(-1) x min(-1)), and [L-cit] (58+/-8 nM). Isoflurane slightly increased CF but not NO. Anesthetics did not alter the bradykinin-induced CF, NO slope relationship, or change [L-cit]. In erythrocyte-perfused hearts, isoflurane also did not alter the bradykinin-induced increase in CF and decrease in percentage of oxygen extracted.
CONCLUSIONS: This is the first study to simultaneously measure CF with bradykinin-induced changes in [NO] and [L-cit] in the presence of halothane, isoflurane, and sevoflurane in intact hearts. The study shows for the first time that volatile anesthetics do not alter the CF to NO relationship and suggests that NO production, NO release, and NO vasodilatory effects mediated by the eNOS cGMP pathway are not significantly affected by anesthetics in crystalloid or erythrocyte-perfused guinea pig hearts.
Author List
Fujita S, Roerig DL, Chung WW, Bosnjak ZJ, Stowe DFAuthors
Zeljko Bosnjak PhD, MS Emeritus Professor in the Medicine department at Medical College of WisconsinDavid F. Stowe PhD, MA, MA Emeritus Professor in the Anesthesiology department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
Anesthetics, InhalationAnimals
Bradykinin
Citrulline
Endothelium, Vascular
Guinea Pigs
Heart
Hemodynamics
Hydrogen-Ion Concentration
In Vitro Techniques
Myocardium
Nitric Oxide
Oxygen Consumption









