VOLATILE ANESTHETICS DO NOT ALTER BRADYKININ-INDUCED RELEASE OF NITRIC-OXIDE OR L-CITRULLINE IN CRYSTALLOID PERFUSED GUINEA-PIG HEARTS

Background: Nitric oxide (NO) and L-citrulline (L-cit) are released by endothelial NO synthase (eNOS) to induce vasodilation via guanylyl cy clase and cyclic guanosine monophosphate (cGMP). Volatile anesthetics directly reduce vascular muscle tone, but their effects on the eNOS cG MP pathway is controversial. The aim of this study was to examine the effects of anesthetics on bradykinin-induced increases in now, NO, and L-cit in isolated hearts. Methods: Guinea pig hearts were isolated, p erfused at 55 mmHg with a crystalloid or erythrocyte perfusate at 37 d egrees C, and heart rate, left ventricular pressure, coronary flow (CF ), effluent pH, and oxygen tension were monitored. Effluent [NO] was m easured by a Clark-type electrode (sensitivity greater than or equal t o 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 mu ch as 100 rm bradykinin to induce increases in CF and effluent release of NO and L-cit. Results: In crystalloid-perfused hearts, 10 nM brady kinin produced maximal concentration-dependent increases in CF (87 +/- 2%), [NO] (24 +/- 4 nM), NO release (128 +/- 18 pmol.g.(-1) 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 rela tionship, or change [L-cit]. in erythrocyte-perfused hearts, isofluran e also did not alter the bradykinln-induced increase in CF and decreas e in percentage of oxygen extracted. Conclusions: This is the first st udy to simultaneously measure CF with bradykinin-induced changes in [N O] and [L-cit] in the presence of halothane, isoflurane, and sevoflura ne in intact hearts. The study shows for the first time that volatile anesthetics do not alter the CF to NO relationship and suggests that N O production, NO release, and NO vasodilatory effects mediated by the eNOS cGMP pathway are not significantly affected by anesthetics in cry stalloid or erythrocyte-perfused guinea pig hearts.