Nitric Oxide-Mediated Hypotensive Effects of Sevoflurane in Rats

Background: Hypotension during general anesthesia increases perioperative morbidity and mortality. Sensitivity to sevoflurane anesthesia is reduced in mice deficient in guanylate cyclase-1, suggesting nitric oxide (NO)-cyclic guanosine monophosphate (cGMP) pathway involvement. Here, we investigated whether sevoflurane induces hypotension via NO-cGMP activation. Methods: Blood pressure, heart rate, and temperature were monitored in telemetry-implanted, spontaneously breathing male Sprague-Dawley rats during sevoflurane administration at 2.0% or 4.5% (20 min). Sevoflurane was administered to the intubated and mechanically ventilated rats and cardiac blood was withdrawn. Plasma and erythrocytic nitrite/nitrate and cGMP levels were measured using high-performance liquid chromatography and enzyme-linked immunosorbent assays, respectively. Results: Hypotension was induced in a concentration-dependent manner, and increases in heart rate were more pronounced with 2.0% sevoflurane than with 4.5%. Plasma nitrate levels were significantly higher with 2.0% than 4.5% (14.1 ± 2.7 μM vs. 10.7 ± 1.0 μM; p = 0.03). No differences in nitrite or cGMP were observed between the two groups. Conclusions: Sevoflurane's hypotensive effects are accompanied by increases in plasma nitrate levels, which is indicative of systemic NO generation. However, the lack of changes in circulating nitrite/cGMP levels implies that sevoflurane-induced hypotension also involves NO-cGMP-independent pathways. Further studies need to elucidate the underlying mechanisms.